viernes, 14 de mayo de 2010
jueves, 7 de enero de 2010
Los priones siguen la ley de Darwin
Estas proteínas mutadas evolucionan para adaptarse al entorno y desarrollar resistencias a fármacos
Los priones están asociados a 20 enfermedades neurodegenerativas en seres humanos y animales, como la enfermedad de las vacas locas o el mal de Creutzfeldt-Jakob. Científicos del Instituto de Investigación Scripps de Florida (EE UU) han descubierto ahora que estas variantes patogénicas de ciertas proteínas son capaces de evolucionar a pesar de no contener ni ADN ni ARN.La investigación, publicada en el último número de la revista Science.
El estudio ha demostrado que los priones pueden mutar para adaptarse al entorno y desarrollar resistencia a fármacos, un fenómeno que hasta ahora sólo sucedía en bacterias y virus. "Se produce el mismo proceso de la mutación y del cambio adaptativo en los priones que en los virus", afirma Charles Weissmann, primer firmante del trabajo y director del departamento de Infectología de Scripps. Esto significa que el patrón evolutivo darviniano es universalmente activo. En los virus, la mutación está ligada a los cambios en la secuencia del ácido nucleico que lleva a la resistencia a los tratamientos farmacológicos. Ahora, esta adaptabilidad ha bajado al nivel de los priones y al plegamiento de la proteína: "Está claro que no es necesario el ácido nucleico para el proceso de la evolución", añade el científico.
Los científicos cultivaron una cepa de priones de neuronas en presencia del compuesto swainsonina, que se encuentra en plantas y hongos, y que ha demostrado que inhibe ciertas cepas de priones. Una pequeña porción de esos priones resistieron al compuesto, y esa variedad acabó por convertirse en la población mayoritaria. De vuelta al cerebro, los priones celulares adaptados asumieron de nuevo el control de la población de priones.
Los priones, que están compuestos solamente de proteína, están clasificados por distintas cepas, originalmente caracterizadas por su tiempo de incubación y la enfermedad que causan. Pero tienen la capacidad de reproducirse, a pesar de que no contienen genes. Las células de los mamíferos producen normalmente la proteína celular o PrPC del prión. Durante la infección, la proteína dividida de forma defectuosa, conocida como PrPSc, convierte al prión húesped en formas tóxicas al cambiar su forma y composición. "Se pensaba que una vez que la proteína celular del prión se convertía en la forma anormal, no había más cambio", dijo Weissmann. Pero al transmitir priones de las ovejas a los ratones, se observó cómo se convirtieron en más virulentos. "Ahora se sabe que los priones anormales se multiplican y crean variantes, quizás a un bajo nivel inicialmente, pero una vez transferidos a un nuevo húesped, la selección natural elegirá las variantes más virulentas y agresivas".
Los investigadores creen que los resultados del trabajo sugieren la necesidad de buscar estrategias terapeúticas distintas a las normales. Por ejemplo, en vez de desarrollar fármacos para combatir proteínas anormales, con el riesgo de que se desarrollen variantes más virulentas o acabar interfiriendo en otros procesos fisiológicos críticos, podría ser más eficiente intentar limitar la fuente de priones producidos normalmente; es decir, sería como reducir la cantidad de combustible que alimenta ese fuego
Los priones están asociados a 20 enfermedades neurodegenerativas en seres humanos y animales, como la enfermedad de las vacas locas o el mal de Creutzfeldt-Jakob. Científicos del Instituto de Investigación Scripps de Florida (EE UU) han descubierto ahora que estas variantes patogénicas de ciertas proteínas son capaces de evolucionar a pesar de no contener ni ADN ni ARN.La investigación, publicada en el último número de la revista Science.
El estudio ha demostrado que los priones pueden mutar para adaptarse al entorno y desarrollar resistencia a fármacos, un fenómeno que hasta ahora sólo sucedía en bacterias y virus. "Se produce el mismo proceso de la mutación y del cambio adaptativo en los priones que en los virus", afirma Charles Weissmann, primer firmante del trabajo y director del departamento de Infectología de Scripps. Esto significa que el patrón evolutivo darviniano es universalmente activo. En los virus, la mutación está ligada a los cambios en la secuencia del ácido nucleico que lleva a la resistencia a los tratamientos farmacológicos. Ahora, esta adaptabilidad ha bajado al nivel de los priones y al plegamiento de la proteína: "Está claro que no es necesario el ácido nucleico para el proceso de la evolución", añade el científico.
Los científicos cultivaron una cepa de priones de neuronas en presencia del compuesto swainsonina, que se encuentra en plantas y hongos, y que ha demostrado que inhibe ciertas cepas de priones. Una pequeña porción de esos priones resistieron al compuesto, y esa variedad acabó por convertirse en la población mayoritaria. De vuelta al cerebro, los priones celulares adaptados asumieron de nuevo el control de la población de priones.
Los priones, que están compuestos solamente de proteína, están clasificados por distintas cepas, originalmente caracterizadas por su tiempo de incubación y la enfermedad que causan. Pero tienen la capacidad de reproducirse, a pesar de que no contienen genes. Las células de los mamíferos producen normalmente la proteína celular o PrPC del prión. Durante la infección, la proteína dividida de forma defectuosa, conocida como PrPSc, convierte al prión húesped en formas tóxicas al cambiar su forma y composición. "Se pensaba que una vez que la proteína celular del prión se convertía en la forma anormal, no había más cambio", dijo Weissmann. Pero al transmitir priones de las ovejas a los ratones, se observó cómo se convirtieron en más virulentos. "Ahora se sabe que los priones anormales se multiplican y crean variantes, quizás a un bajo nivel inicialmente, pero una vez transferidos a un nuevo húesped, la selección natural elegirá las variantes más virulentas y agresivas".
Los investigadores creen que los resultados del trabajo sugieren la necesidad de buscar estrategias terapeúticas distintas a las normales. Por ejemplo, en vez de desarrollar fármacos para combatir proteínas anormales, con el riesgo de que se desarrollen variantes más virulentas o acabar interfiriendo en otros procesos fisiológicos críticos, podría ser más eficiente intentar limitar la fuente de priones producidos normalmente; es decir, sería como reducir la cantidad de combustible que alimenta ese fuego
martes, 5 de enero de 2010
Better Vision for the World, on a Budget
VEGHEL, the Netherlands — With AIDS, malaria and other diseases costing millions of lives every year, worrying about the vision of people in the developing world may seem like an indulgence.
A study published in a World Health Organization journal in June estimated the cost in lost output at $269 billion a year. Moreover, tackling vision problems early can help prevent later blindness.
Now efforts are under way to find a means of distributing inexpensive glasses on a wide scale. One promising technology is self-adjustable spectacles, which let untrained wearers set the right focus themselves in less than a minute, greatly reducing the need for trained optometrists, who are rarely available in Africa and many parts of Asia. Though these adjustable glasses cannot yet help with conditions like astigmatism, at least 80 percent of refractive errors can be fixed.
At least three organizations are now offering their own versions of low-cost adjustable spectacles. Two are relatively new groups based in the Netherlands that have received little international recognition. The third, based in England and championing a British invention called AdSpecs, has been attracting widespread media attention for more than a decade.
AdSpecs, which allow the corrective power of the glasses to be adjusted by means of a clear fluid injected into the lenses, were developed by Joshua Silver, a physics professor at Oxford University who directs a research institute there called the Center for Vision in the Developing World.
Since introducing the glasses in 1996, Professor Silver has set an ambitious goal of distributing a billion pairs of low-cost adjustable glasses by the year 2020.
In the intervening 13 years, though, only about 30,000 AdSpecs have been distributed; they cost about $19 a pair.
One of the Dutch groups, the Focus on Vision Foundation, says it can produce its Focusspec glasses for about $4 a pair. The group’s founders say the price will drop substantially once the glasses are being made in large volume. They plan to distribute about 30,000 pairs in early 2010, initially in Afghanistan, Ghana and Tanzania.
The other Dutch offering, called U-Specs (universal spectacles), is being promoted by the VU University Medical Center and a charity called the D.O.B. Foundation.
Both Dutch models are based on a design pioneered in the 1960s by Luis W. Alvarez, an American who won a Nobel Prize in physics. The design uses two lenses that slide across each other to alter their focus. U-Specs were initially developed in 2003 by Rob van der Heijde, a physicist at the VU University Amsterdam.
Frederik van Asbeck, a former student of Professor van der Heijde, struck out on his own to develop the Focusspec in 2005. Though the Dutch camps have had sporadic contact, they are not working together.
The tangled provenance of the designs demonstrates the unspoken yet occasionally palpable sense of rivalry among the various camps.
“I view them as good friends,” Professor Silver, the inventor of AdSpecs, said. “We’re not competitors. I’m just rather keen on origins and facts being clearly stated.”
He said they all agreed that the developing world needed a “low-cost design that can be produced at very high volume,” conceding that “none of the enterprises around today can do that.”
But each camp is convinced that it has the best approach to supply the millions or even billions of inexpensive glasses the developing world needs.
Focus on Vision says its advantage is the unique injection-molding process that allows its Focusspec eyeglasses to be made cheaply. It was developed by a Dutch engineer, Ron Kok, who grew wealthy in the 1980s by streamlining the manufacture of compact discs and contact lenses.
Focus on Vision invited Mr. Kok to work that same magic on its glasses. “I saw immediately that you could make it simpler,” he said. “They’re designed to be easy and cheap to produce.”
The U-Specs team emphasizes its scientific pedigree. “We took more of an academic approach, or at least a scientific approach, rather than an entrepreneurial one,” said Sjoerd Hannema, who was in charge of the U-Specs project until the middle of 2009. “Having a university and an eye hospital behind it,” he said, “helps build recognition and authority around this project.”
Mr. Hannema now leads a nonprofit organization called Adaptive Eyewear, which is running a distribution project in Rwanda called Vision for a Nation. It uses a combination of U-Specs, a version of Professor Silver’s lenses and traditional reading glasses.
Although they are not made using Mr. Kok’s special production technique, supporters of U-Specs say they will ultimately cost about the same to produce as the Focusspec.
“It will be around one to two dollars, depending on the quantity,” Mr. Hannema said. “If you make a million glasses, then automatically your cost price goes down dramatically. But then the challenge is where are you going to bring those glasses? Ultimately the cost of distribution is what matters.”
“They’re basically all at the same level,” he said, “and at the first stage of a very complicated journey.”
The Focusspec team contends that it is the closest to reaching mass production. “I think we’re the furthest,” said Dr. Ben van Noort, an ophthalmologist who is president of Focus on Vision. “But we’ll see. As soon as we make a million per year, the price will drop to a euro.”
He suggested that fluid-based spectacles, like those promoted by Professor Silver, were more sensitive to shifts in temperature, which made them less stable, especially in the challenging climates where many of these glasses are to be distributed.
Yet the Focusspec has also had its early problems. In a recent visit to the production facility in Veghel, which is about 50 miles southeast of Amsterdam, the adjustment wheel was not working properly on a large batch of glasses. They had to be repaired before they could be sent to Afghanistan, where they were eventually to be distributed by Dutch soldiers stationed there.
“Once you start to produce them on a large scale, you bump into things like this,” Dr. van Noort said. “It’s trial and error. There’s no handbook for this.”
Professor Silver said his fluid-filled spectacles would eventually cost less as well. “The Focus on Vision work is very interesting in that it shows that significant cost reduction is possible,” he said. “But from my perspective, the jury is still out. There’s no reason why Alvarez would be cheaper” in the long term.
When it comes to choosing sides, many of the charitable groups involved say they are open to whatever glasses do the job. J. Kevin White, a former Marine who runs Global Vision 2020, a foundation that distributes adjustable glasses, said fluid-filled lenses generally offer better optical quality and correct a greater range of refractive error. The Alvarez designs, by contrast, are cheaper, smaller, better-looking and less likely to break.
For his part, Mr. Hannema of Adaptive Eyewear considers the occasional strife between the groups counterproductive.
“Kids in India don’t benefit from that,” he said. “It’s like if Unicef and the Red Cross would quarrel about a patent on a medicine from a hundred years ago.”
A study published in a World Health Organization journal in June estimated the cost in lost output at $269 billion a year. Moreover, tackling vision problems early can help prevent later blindness.
Now efforts are under way to find a means of distributing inexpensive glasses on a wide scale. One promising technology is self-adjustable spectacles, which let untrained wearers set the right focus themselves in less than a minute, greatly reducing the need for trained optometrists, who are rarely available in Africa and many parts of Asia. Though these adjustable glasses cannot yet help with conditions like astigmatism, at least 80 percent of refractive errors can be fixed.
At least three organizations are now offering their own versions of low-cost adjustable spectacles. Two are relatively new groups based in the Netherlands that have received little international recognition. The third, based in England and championing a British invention called AdSpecs, has been attracting widespread media attention for more than a decade.
AdSpecs, which allow the corrective power of the glasses to be adjusted by means of a clear fluid injected into the lenses, were developed by Joshua Silver, a physics professor at Oxford University who directs a research institute there called the Center for Vision in the Developing World.
Since introducing the glasses in 1996, Professor Silver has set an ambitious goal of distributing a billion pairs of low-cost adjustable glasses by the year 2020.
In the intervening 13 years, though, only about 30,000 AdSpecs have been distributed; they cost about $19 a pair.
One of the Dutch groups, the Focus on Vision Foundation, says it can produce its Focusspec glasses for about $4 a pair. The group’s founders say the price will drop substantially once the glasses are being made in large volume. They plan to distribute about 30,000 pairs in early 2010, initially in Afghanistan, Ghana and Tanzania.
The other Dutch offering, called U-Specs (universal spectacles), is being promoted by the VU University Medical Center and a charity called the D.O.B. Foundation.
Both Dutch models are based on a design pioneered in the 1960s by Luis W. Alvarez, an American who won a Nobel Prize in physics. The design uses two lenses that slide across each other to alter their focus. U-Specs were initially developed in 2003 by Rob van der Heijde, a physicist at the VU University Amsterdam.
Frederik van Asbeck, a former student of Professor van der Heijde, struck out on his own to develop the Focusspec in 2005. Though the Dutch camps have had sporadic contact, they are not working together.
The tangled provenance of the designs demonstrates the unspoken yet occasionally palpable sense of rivalry among the various camps.
“I view them as good friends,” Professor Silver, the inventor of AdSpecs, said. “We’re not competitors. I’m just rather keen on origins and facts being clearly stated.”
He said they all agreed that the developing world needed a “low-cost design that can be produced at very high volume,” conceding that “none of the enterprises around today can do that.”
But each camp is convinced that it has the best approach to supply the millions or even billions of inexpensive glasses the developing world needs.
Focus on Vision says its advantage is the unique injection-molding process that allows its Focusspec eyeglasses to be made cheaply. It was developed by a Dutch engineer, Ron Kok, who grew wealthy in the 1980s by streamlining the manufacture of compact discs and contact lenses.
Focus on Vision invited Mr. Kok to work that same magic on its glasses. “I saw immediately that you could make it simpler,” he said. “They’re designed to be easy and cheap to produce.”
The U-Specs team emphasizes its scientific pedigree. “We took more of an academic approach, or at least a scientific approach, rather than an entrepreneurial one,” said Sjoerd Hannema, who was in charge of the U-Specs project until the middle of 2009. “Having a university and an eye hospital behind it,” he said, “helps build recognition and authority around this project.”
Mr. Hannema now leads a nonprofit organization called Adaptive Eyewear, which is running a distribution project in Rwanda called Vision for a Nation. It uses a combination of U-Specs, a version of Professor Silver’s lenses and traditional reading glasses.
Although they are not made using Mr. Kok’s special production technique, supporters of U-Specs say they will ultimately cost about the same to produce as the Focusspec.
“It will be around one to two dollars, depending on the quantity,” Mr. Hannema said. “If you make a million glasses, then automatically your cost price goes down dramatically. But then the challenge is where are you going to bring those glasses? Ultimately the cost of distribution is what matters.”
“They’re basically all at the same level,” he said, “and at the first stage of a very complicated journey.”
The Focusspec team contends that it is the closest to reaching mass production. “I think we’re the furthest,” said Dr. Ben van Noort, an ophthalmologist who is president of Focus on Vision. “But we’ll see. As soon as we make a million per year, the price will drop to a euro.”
He suggested that fluid-based spectacles, like those promoted by Professor Silver, were more sensitive to shifts in temperature, which made them less stable, especially in the challenging climates where many of these glasses are to be distributed.
Yet the Focusspec has also had its early problems. In a recent visit to the production facility in Veghel, which is about 50 miles southeast of Amsterdam, the adjustment wheel was not working properly on a large batch of glasses. They had to be repaired before they could be sent to Afghanistan, where they were eventually to be distributed by Dutch soldiers stationed there.
“Once you start to produce them on a large scale, you bump into things like this,” Dr. van Noort said. “It’s trial and error. There’s no handbook for this.”
Professor Silver said his fluid-filled spectacles would eventually cost less as well. “The Focus on Vision work is very interesting in that it shows that significant cost reduction is possible,” he said. “But from my perspective, the jury is still out. There’s no reason why Alvarez would be cheaper” in the long term.
When it comes to choosing sides, many of the charitable groups involved say they are open to whatever glasses do the job. J. Kevin White, a former Marine who runs Global Vision 2020, a foundation that distributes adjustable glasses, said fluid-filled lenses generally offer better optical quality and correct a greater range of refractive error. The Alvarez designs, by contrast, are cheaper, smaller, better-looking and less likely to break.
For his part, Mr. Hannema of Adaptive Eyewear considers the occasional strife between the groups counterproductive.
“Kids in India don’t benefit from that,” he said. “It’s like if Unicef and the Red Cross would quarrel about a patent on a medicine from a hundred years ago.”
martes, 29 de diciembre de 2009
In New Way to Edit DNA, Hope for Treating Disease
Only one man seems to have ever been cured of AIDS, a patient who also had leukemia. To treat the leukemia, he received a bone marrow transplant in Berlin from a donor who, as luck would have it, was naturally immune to the AIDS virus.
If that natural mutation could be mimicked in human blood cells, patients could be endowed with immunity to the deadly virus. But there is no effective way of making precise alterations in human DNA.
That may be about to change, if a powerful new technique for editing the genetic text proves to be safe and effective. At the University of Pennsylvania, Dr. Carl June and colleagues have used the technique to disrupt a gene in patients’ T cells, the type attacked by the AIDS virus. They have then infused those cells back into the body. A clinical trial is now under way to see if the treated cells will reconstitute a patient’s immune system and defeat the virus.
The technique, which depends on natural agents called zinc fingers, may revive the lagging fortunes of gene therapy because it overcomes the inability to insert new genes at a chosen site. Other researchers plan to use the zinc finger technique to provide genetic treatments for diseases like bubble-boy disease, hemophilia and sickle-cell anemia.
In principle, the zinc finger approach should work on almost any site on any chromosome of any plant or animal. If so, it would provide a general method for generating new crop plants, treating many human diseases, and even making inheritable changes in human sperm or eggs, should such interventions ever be regarded as ethically justifiable.
Zinc fingers are essential components of proteins used by living cells to turn genes on and off. Their name derives from the atom of zinc that holds two loops of protein together to form a “finger.” Because the fingers recognize specific sequences of DNA, they guide the control proteins to the exact site where their target gene begins.
After many years of development, biologists have learned how to modify nature’s DNA recognition system into a general system for manipulating genes. Each natural zinc finger recognizes a set of three letters, or bases, on the DNA molecule. By stringing three or four fingers together, researchers can generate artificial proteins that match a particular site.
The new system has been developed by a small biotech company, Sangamo BioSciences of Richmond, Calif., and, to some degree separately, by academic researchers who belong to the Zinc Finger Consortium.
Sangamo was founded in 1995 by Edward O. Lanphier II, a former executive with a gene therapy company. Reading an article by Aaron Klug, the British crystallographer who discovered the zinc finger design, he saw the technique’s potential for genetic manipulation. He bought a company Dr. Klug had founded and worked with him and researchers like Carl O. Pabo to improve the technique and develop combinations of zinc fingers to match any sequence of DNA letters.
“We now have a full alphabet of zinc fingers,” Mr. Lanphier said, “but when we started the company it was like typing a novel with two fingers.”
Zinc finger proteins have many potential uses. One is to link them to agents that turn on or turn off the gene at the site recognized by the fingers.
More powerfully, the zinc fingers can be deployed as a word processing system for cutting and pasting genetic text. Two sets of zinc fingers are attached to a protein that cuts the DNA in between the two sites matched by the fingers. The cell quickly repairs the break but sometimes in a way that disrupts the gene. This is the approach used in destroying the gene for the receptor used by the AIDS virus to gain entry to white blood cells.
Or, if DNA for a new gene is inserted into a cell at the same time as the zinc fingers that scissor the DNA, the new gene will be incorporated by the cell’s repair system into the DNA at the break site. Most gene therapy techniques use a virus to carry new genes into a cell but cannot direct the virus to insert genes at a specific site.
“I think it’s a broadly applicable technology which has already allowed experiments that would not have been possible before,” said J. Keith Joung, a biologist who designs zinc finger proteins at the Massachusetts General Hospital.
Daniel F. Voytas, a plant geneticist at the University of Minnesota, said the zinc finger technique would allow breeders to change the oil composition of any plant, the types of carbohydrates produced or the way carbon dioxide is captured. “We can go in and make any change we want to any plant species,” Dr. Voytas said.
Zinc fingers can also be used for “trait stacking,” the positioning of several beneficial genes at a single site. This avoids heavy regulatory costs because genetically altered plants must be tested for safety for each site that is modified.
The zinc finger technology has taken many years to prepare because of the difficulty of designing the fingers and also of preventing them from cutting the genome in the wrong places. Only a handful of laboratories are currently using the technique, but proponents expect to see rapid growth.
The Zinc Finger Consortium, founded by Dr. Joung and Dr. Voytas, makes the method available free, and researchers need only pay for materials. But there are some 200 steps in Dr. Joung’s recipe for making zinc fingers, and it takes time and dedication to do them all correctly.
The alternative is to buy zinc fingers. Sangamo has a commanding patent position and has licensed Sigma-Aldrich, a large life science company in St. Louis, to make zinc finger proteins for researchers. Sigma-Aldrich’s charge for a zinc finger protein that cuts the genome at the site of your choice is $39,000, with a discount for academic researchers. Zinc fingers that cut well-known human genes cost $12,000. Sigma-Aldrich has used the technology to generate rats with genetic defects that mimic human disease. A schizophrenic rat can be had for $100.
David Smoller, president of Sigma-Aldrich’s biotechnology unit, licensed the technology from Sangamo in 2006 when he felt the company had proved it worked. “This technology is just amazing,” Dr. Smoller said. “It’s a game changer.”
Sangamo has licensed the use of zinc fingers to Dow Agrosciences for creating new crop plants, and has reserved medical uses for itself. It has four Phase 2 clinical trials in progress, including treatments for diabetic neuropathy and amyotrophic lateral sclerosis.
In an ambitious effort to cure AIDS, Sangamo and the University of Pennsylvania started a clinical trial in February.
The AIDS virus enters the T cells of the immune system by latching on to a receptor called CCR5, but about 10 percent of Europeans have a mutation that disables the CCR5 gene. People who inherit two disabled copies of the gene do not have CCR5 on the surface of their T cells, so the AIDS virus has nothing to grab. These people are highly resistant to H.I.V.
In the zinc finger approach, the patient’s T cells are removed, and zinc finger scissors are used to disable the CCR5 gene. The treated cells are allowed to multiply, then reinjected into the patient. In experiments with mice, the treated cells turned out to have a strong natural advantage over the untreated ones, since those are under constant attack by the AIDS virus.
Whether or not zinc fingers will make gene therapy practical remains to be seen. “It’s a little too early to know since clinical trials are in their early stages,” said Dr. Katherine A. High, a hemophilia expert at the University of Pennsylvania.
Dr. Matthew H. Porteus, a pediatric geneticist at the University of Texas, said, “I think it has the potential to solve a lot of the problems that have plagued the gene therapy field.” But Dr. Porteus noted that even the most carefully designed zinc fingers seemed to do some snipping away from their target site, a potentially serious safety problem.
Zinc fingers could be the gift that stem cell researchers have been waiting for. Stem cells taken from a patient may need to be genetically corrected before use, but until now there had been no way of doing so.
Dr. Rudolf Jaenisch, a stem cell expert at the Whitehead Institute in Cambridge, Mass., reported in August that he had successfully singled out three genes in induced embryonic stem cells with the help of zinc finger scissors designed by Sangamo. “This is a really important tool for human embryonic stem cells,” Dr. Jaenisch said. The technology has not yet reached perfection. Some of the zinc fingers Sangamo provided “worked beautifully,” he said, but some did not.
Zinc fingers may also make technically possible a morally fraught procedure that has been merely a theoretical possibility — the alteration of the human germ line, meaning the egg or sperm cells. Genetic changes made in current gene therapy are to body cells, and they would die with the individual. But changes made to the germ line would be inherited. Many ethicists and others say this is a bridge that should not be crossed, since altering the germ line, even if justifiable for medical reasons, would lower the barrier to other kinds of change.
Several scientists were reluctant to discuss the issue, or dismissed it by saying that even zinc fingers did not meet the error-free standards that would be required for germ-line engineering. But zinc finger scissors are so efficient that only 5 to 10 embryos need be treated to get one with the desired result. This could make it practical to alter the germ line.
Since the germ lines of rats and zebra fish have already been altered with zinc finger scissors, “in principle there is no reason why a similar strategy could not be used to modify the human germ line,” Dr. Porteus said. The kind of disease that might be better treated in the germ line, if ethically acceptable, is cystic fibrosis, which affects many different tissues.
The disease could be corrected in unfertilized eggs, using the zinc finger technique, Dr. Porteus said. But he added, “I don’t think our society is ready for someone to propose this.”
If that natural mutation could be mimicked in human blood cells, patients could be endowed with immunity to the deadly virus. But there is no effective way of making precise alterations in human DNA.
That may be about to change, if a powerful new technique for editing the genetic text proves to be safe and effective. At the University of Pennsylvania, Dr. Carl June and colleagues have used the technique to disrupt a gene in patients’ T cells, the type attacked by the AIDS virus. They have then infused those cells back into the body. A clinical trial is now under way to see if the treated cells will reconstitute a patient’s immune system and defeat the virus.
The technique, which depends on natural agents called zinc fingers, may revive the lagging fortunes of gene therapy because it overcomes the inability to insert new genes at a chosen site. Other researchers plan to use the zinc finger technique to provide genetic treatments for diseases like bubble-boy disease, hemophilia and sickle-cell anemia.
In principle, the zinc finger approach should work on almost any site on any chromosome of any plant or animal. If so, it would provide a general method for generating new crop plants, treating many human diseases, and even making inheritable changes in human sperm or eggs, should such interventions ever be regarded as ethically justifiable.
Zinc fingers are essential components of proteins used by living cells to turn genes on and off. Their name derives from the atom of zinc that holds two loops of protein together to form a “finger.” Because the fingers recognize specific sequences of DNA, they guide the control proteins to the exact site where their target gene begins.
After many years of development, biologists have learned how to modify nature’s DNA recognition system into a general system for manipulating genes. Each natural zinc finger recognizes a set of three letters, or bases, on the DNA molecule. By stringing three or four fingers together, researchers can generate artificial proteins that match a particular site.
The new system has been developed by a small biotech company, Sangamo BioSciences of Richmond, Calif., and, to some degree separately, by academic researchers who belong to the Zinc Finger Consortium.
Sangamo was founded in 1995 by Edward O. Lanphier II, a former executive with a gene therapy company. Reading an article by Aaron Klug, the British crystallographer who discovered the zinc finger design, he saw the technique’s potential for genetic manipulation. He bought a company Dr. Klug had founded and worked with him and researchers like Carl O. Pabo to improve the technique and develop combinations of zinc fingers to match any sequence of DNA letters.
“We now have a full alphabet of zinc fingers,” Mr. Lanphier said, “but when we started the company it was like typing a novel with two fingers.”
Zinc finger proteins have many potential uses. One is to link them to agents that turn on or turn off the gene at the site recognized by the fingers.
More powerfully, the zinc fingers can be deployed as a word processing system for cutting and pasting genetic text. Two sets of zinc fingers are attached to a protein that cuts the DNA in between the two sites matched by the fingers. The cell quickly repairs the break but sometimes in a way that disrupts the gene. This is the approach used in destroying the gene for the receptor used by the AIDS virus to gain entry to white blood cells.
Or, if DNA for a new gene is inserted into a cell at the same time as the zinc fingers that scissor the DNA, the new gene will be incorporated by the cell’s repair system into the DNA at the break site. Most gene therapy techniques use a virus to carry new genes into a cell but cannot direct the virus to insert genes at a specific site.
“I think it’s a broadly applicable technology which has already allowed experiments that would not have been possible before,” said J. Keith Joung, a biologist who designs zinc finger proteins at the Massachusetts General Hospital.
Daniel F. Voytas, a plant geneticist at the University of Minnesota, said the zinc finger technique would allow breeders to change the oil composition of any plant, the types of carbohydrates produced or the way carbon dioxide is captured. “We can go in and make any change we want to any plant species,” Dr. Voytas said.
Zinc fingers can also be used for “trait stacking,” the positioning of several beneficial genes at a single site. This avoids heavy regulatory costs because genetically altered plants must be tested for safety for each site that is modified.
The zinc finger technology has taken many years to prepare because of the difficulty of designing the fingers and also of preventing them from cutting the genome in the wrong places. Only a handful of laboratories are currently using the technique, but proponents expect to see rapid growth.
The Zinc Finger Consortium, founded by Dr. Joung and Dr. Voytas, makes the method available free, and researchers need only pay for materials. But there are some 200 steps in Dr. Joung’s recipe for making zinc fingers, and it takes time and dedication to do them all correctly.
The alternative is to buy zinc fingers. Sangamo has a commanding patent position and has licensed Sigma-Aldrich, a large life science company in St. Louis, to make zinc finger proteins for researchers. Sigma-Aldrich’s charge for a zinc finger protein that cuts the genome at the site of your choice is $39,000, with a discount for academic researchers. Zinc fingers that cut well-known human genes cost $12,000. Sigma-Aldrich has used the technology to generate rats with genetic defects that mimic human disease. A schizophrenic rat can be had for $100.
David Smoller, president of Sigma-Aldrich’s biotechnology unit, licensed the technology from Sangamo in 2006 when he felt the company had proved it worked. “This technology is just amazing,” Dr. Smoller said. “It’s a game changer.”
Sangamo has licensed the use of zinc fingers to Dow Agrosciences for creating new crop plants, and has reserved medical uses for itself. It has four Phase 2 clinical trials in progress, including treatments for diabetic neuropathy and amyotrophic lateral sclerosis.
In an ambitious effort to cure AIDS, Sangamo and the University of Pennsylvania started a clinical trial in February.
The AIDS virus enters the T cells of the immune system by latching on to a receptor called CCR5, but about 10 percent of Europeans have a mutation that disables the CCR5 gene. People who inherit two disabled copies of the gene do not have CCR5 on the surface of their T cells, so the AIDS virus has nothing to grab. These people are highly resistant to H.I.V.
In the zinc finger approach, the patient’s T cells are removed, and zinc finger scissors are used to disable the CCR5 gene. The treated cells are allowed to multiply, then reinjected into the patient. In experiments with mice, the treated cells turned out to have a strong natural advantage over the untreated ones, since those are under constant attack by the AIDS virus.
Whether or not zinc fingers will make gene therapy practical remains to be seen. “It’s a little too early to know since clinical trials are in their early stages,” said Dr. Katherine A. High, a hemophilia expert at the University of Pennsylvania.
Dr. Matthew H. Porteus, a pediatric geneticist at the University of Texas, said, “I think it has the potential to solve a lot of the problems that have plagued the gene therapy field.” But Dr. Porteus noted that even the most carefully designed zinc fingers seemed to do some snipping away from their target site, a potentially serious safety problem.
Zinc fingers could be the gift that stem cell researchers have been waiting for. Stem cells taken from a patient may need to be genetically corrected before use, but until now there had been no way of doing so.
Dr. Rudolf Jaenisch, a stem cell expert at the Whitehead Institute in Cambridge, Mass., reported in August that he had successfully singled out three genes in induced embryonic stem cells with the help of zinc finger scissors designed by Sangamo. “This is a really important tool for human embryonic stem cells,” Dr. Jaenisch said. The technology has not yet reached perfection. Some of the zinc fingers Sangamo provided “worked beautifully,” he said, but some did not.
Zinc fingers may also make technically possible a morally fraught procedure that has been merely a theoretical possibility — the alteration of the human germ line, meaning the egg or sperm cells. Genetic changes made in current gene therapy are to body cells, and they would die with the individual. But changes made to the germ line would be inherited. Many ethicists and others say this is a bridge that should not be crossed, since altering the germ line, even if justifiable for medical reasons, would lower the barrier to other kinds of change.
Several scientists were reluctant to discuss the issue, or dismissed it by saying that even zinc fingers did not meet the error-free standards that would be required for germ-line engineering. But zinc finger scissors are so efficient that only 5 to 10 embryos need be treated to get one with the desired result. This could make it practical to alter the germ line.
Since the germ lines of rats and zebra fish have already been altered with zinc finger scissors, “in principle there is no reason why a similar strategy could not be used to modify the human germ line,” Dr. Porteus said. The kind of disease that might be better treated in the germ line, if ethically acceptable, is cystic fibrosis, which affects many different tissues.
The disease could be corrected in unfertilized eggs, using the zinc finger technique, Dr. Porteus said. But he added, “I don’t think our society is ready for someone to propose this.”
martes, 3 de noviembre de 2009
Una nueva etapa en el tratamiento de la artritis reumatoide
La revista 'The Lancet' publica una revisión de los estudios publicados hasta la fecha sobre las nuevas terapias que se han empezado a utilizar contra la artritis reumatoide. Según este informe, los últimos fármacos desarrollados han abierto el abanico de posibilidades a los pacientes. Sin embargo, todavía son necesarias más investigaciones que por un lado analicen los efectos secundarios a largo plazo de estos tratamientos y por otro aporten nuevas dianas en la lucha contra esta enfermedad.
Todavía no se conoce la causa que origina la artritis reumatoide. Se sabe que la enfermedad está relacionada con una activación excesiva del sistema inmunológico, que genera una producción de sustancias que inducen a la inflamación y destrucción del hueso de las articulaciones.
En los últimos años, se han desarrollado tres tipos de fármacos biológicos que van dirigidos a ciertas moléculas (antígenos) presentes en las células del sistema inmunológico o a proteínas producidas por ellas: abatacept, rituximab y tocilizumab. Los dos primeros ya han sido aprobados por las autoridades sanitarias de Estados Unidos y Europa (la FDA y la EMEA), el tercero se encuentra en fase III de investigación y todavía no se ha comercializado.
Abatacept actúa bloqueando dos moléculas, la CD80 o la CD86, que estimulan la activación de los linfocitos T (células del sistema inmunológico), mientras que rituximab actúa contra el antígeno CD20 que reduce los linfocitos B y tocilizumab bloquea la acción de la interleuquina 6, un tipo de proteínas que activa los linfocitos T y B.
Según la revisión, realizada por reumatólogos de Universidad de Viena, del Hospital Hietzing, también en Viena (Austria), del Centro Médico Cedars-Sinai de Los Ángeles, California (EEUU) y del Chapel Allerton Hospital en Leeds (Reino Unido), para considerar si estos fármacos son eficaces se debe alcanzar una máxima respuesta clínica y una reducción en la actividad de la enfermedad.
Y eso es lo que se ha valorado en los diferentes estudios realizados hasta la fecha. Los ensayos que evaluaron rituximab muestran que redujo en más de un 50% los síntomas de la artritis reumatoide en un tercio de los pacientes en los que se probó la terapia.
En cuanto a los efectos secundarios detectados, la revisión señala reacciones tras la infusión del medicamento en el 30-35% de los participantes. También se registraron infecciones más graves en las personas tratadas con rituximab que en aquellas que había recibido placebo. Además, la actividad sobre los linfocitos B disminuye con el tiempo por lo que se requiere volver a tratar a los pacientes para mantener su eficacia.
Eficacia y efectos secundarios
Una terapia combinada de metotrexato y 10mg de abatacept logró a los seis meses una mejoría del 50% de los síntomas de la artritis reumatoide en el 40% de los pacientes. Además, se detectó una mejoría mediante pruebas radiográficas. Los efectos secundarios más frecuentes han sido cefalea, nasofaringitis, mareos e hipertensión, sobre todo durante la primera hora tras su administración. Trastornos como neumonía, celulitis, diverticulitis o infecciones urinarias también aparecieron con más frecuencia con este fármaco.
No se recomienda la combinación de abatacept con los antiTNF ni con otros agentes biológicos debido a que la aparición de efectos secundarios se multiplica y a que no se mejora la eficacia del tratamiento.
Estudios en laboratorio y con animales observaron que el bloqueo de la interleuquina 6 prevenía la formación de osteoclastos, células que destruyen el hueso. Tocilizumab, que actúa inhibiendo esta proteína, combinado con metotrexato reduce en un 50% los síntomas de la artritis reumatoide en más de un 40% de los pacientes. Esta terapia generó en un pequeño porcentaje de los pacientes cefalea, erupciones en la piel y fiebre. También se detectó un aumento de los niveles de colesterol y de enzimas hepáticas.
Cuanto antes, mejor
Estas terapias podrían utilizarse principalmente en pacientes que presentan síntomas de artritis reumatoide a pesar de estar utilizando inhibidores del factor de nectrosis tumoral (los antiTNF) y metotrexato, que constituyen la terapia clásica y de inicio frente a la enfermedad.
El tratamiento debe comenzarse cuanto antes porque, tal y como indicaban recientemente reumatólogos españoles en el IV Simposio de Artritis Reumatoide, no tratar la enfermedad no sólo afectará a las articulaciones sino que conllevará complicaciones en otros órganos como el corazón.
"Los nuevos fármacos discutidos aquí [en la revisión] expanden claramente el número de terapias contra la artritis reumatoide. Sin embargo, más investigaciones serán necesarias como una comparación directa entre metotrexato y los inhibidores TNF", señalan los autores.
No obstante, los pacientes con artritis reumatoide verán a lo largo de los próximos meses y años los resultados de numerosos estudios que se están llevando a cabo evaluando nuevos fármacos como los que actúan frente a la interleuquina 1 beta, los nuevos inhibidores TNF o los agentes que interfieren únicamente en la activación del osteoclasto.
Qué fármacos deberán utilizarse primero o por qué los pacientes responden a un agente pero no a otro incluso cuando los tratamientos están dirigidos a la misma molécula, son preguntas que deberán contestarse en futuras investigaciones para las que se requerirán inversiones y dedicación, tal y como reclaman los autores de la revisión.
Todavía no se conoce la causa que origina la artritis reumatoide. Se sabe que la enfermedad está relacionada con una activación excesiva del sistema inmunológico, que genera una producción de sustancias que inducen a la inflamación y destrucción del hueso de las articulaciones.
En los últimos años, se han desarrollado tres tipos de fármacos biológicos que van dirigidos a ciertas moléculas (antígenos) presentes en las células del sistema inmunológico o a proteínas producidas por ellas: abatacept, rituximab y tocilizumab. Los dos primeros ya han sido aprobados por las autoridades sanitarias de Estados Unidos y Europa (la FDA y la EMEA), el tercero se encuentra en fase III de investigación y todavía no se ha comercializado.
Abatacept actúa bloqueando dos moléculas, la CD80 o la CD86, que estimulan la activación de los linfocitos T (células del sistema inmunológico), mientras que rituximab actúa contra el antígeno CD20 que reduce los linfocitos B y tocilizumab bloquea la acción de la interleuquina 6, un tipo de proteínas que activa los linfocitos T y B.
Según la revisión, realizada por reumatólogos de Universidad de Viena, del Hospital Hietzing, también en Viena (Austria), del Centro Médico Cedars-Sinai de Los Ángeles, California (EEUU) y del Chapel Allerton Hospital en Leeds (Reino Unido), para considerar si estos fármacos son eficaces se debe alcanzar una máxima respuesta clínica y una reducción en la actividad de la enfermedad.
Y eso es lo que se ha valorado en los diferentes estudios realizados hasta la fecha. Los ensayos que evaluaron rituximab muestran que redujo en más de un 50% los síntomas de la artritis reumatoide en un tercio de los pacientes en los que se probó la terapia.
En cuanto a los efectos secundarios detectados, la revisión señala reacciones tras la infusión del medicamento en el 30-35% de los participantes. También se registraron infecciones más graves en las personas tratadas con rituximab que en aquellas que había recibido placebo. Además, la actividad sobre los linfocitos B disminuye con el tiempo por lo que se requiere volver a tratar a los pacientes para mantener su eficacia.
Eficacia y efectos secundarios
Una terapia combinada de metotrexato y 10mg de abatacept logró a los seis meses una mejoría del 50% de los síntomas de la artritis reumatoide en el 40% de los pacientes. Además, se detectó una mejoría mediante pruebas radiográficas. Los efectos secundarios más frecuentes han sido cefalea, nasofaringitis, mareos e hipertensión, sobre todo durante la primera hora tras su administración. Trastornos como neumonía, celulitis, diverticulitis o infecciones urinarias también aparecieron con más frecuencia con este fármaco.
No se recomienda la combinación de abatacept con los antiTNF ni con otros agentes biológicos debido a que la aparición de efectos secundarios se multiplica y a que no se mejora la eficacia del tratamiento.
Estudios en laboratorio y con animales observaron que el bloqueo de la interleuquina 6 prevenía la formación de osteoclastos, células que destruyen el hueso. Tocilizumab, que actúa inhibiendo esta proteína, combinado con metotrexato reduce en un 50% los síntomas de la artritis reumatoide en más de un 40% de los pacientes. Esta terapia generó en un pequeño porcentaje de los pacientes cefalea, erupciones en la piel y fiebre. También se detectó un aumento de los niveles de colesterol y de enzimas hepáticas.
Cuanto antes, mejor
Estas terapias podrían utilizarse principalmente en pacientes que presentan síntomas de artritis reumatoide a pesar de estar utilizando inhibidores del factor de nectrosis tumoral (los antiTNF) y metotrexato, que constituyen la terapia clásica y de inicio frente a la enfermedad.
El tratamiento debe comenzarse cuanto antes porque, tal y como indicaban recientemente reumatólogos españoles en el IV Simposio de Artritis Reumatoide, no tratar la enfermedad no sólo afectará a las articulaciones sino que conllevará complicaciones en otros órganos como el corazón.
"Los nuevos fármacos discutidos aquí [en la revisión] expanden claramente el número de terapias contra la artritis reumatoide. Sin embargo, más investigaciones serán necesarias como una comparación directa entre metotrexato y los inhibidores TNF", señalan los autores.
No obstante, los pacientes con artritis reumatoide verán a lo largo de los próximos meses y años los resultados de numerosos estudios que se están llevando a cabo evaluando nuevos fármacos como los que actúan frente a la interleuquina 1 beta, los nuevos inhibidores TNF o los agentes que interfieren únicamente en la activación del osteoclasto.
Qué fármacos deberán utilizarse primero o por qué los pacientes responden a un agente pero no a otro incluso cuando los tratamientos están dirigidos a la misma molécula, son preguntas que deberán contestarse en futuras investigaciones para las que se requerirán inversiones y dedicación, tal y como reclaman los autores de la revisión.
Nanotubes May Heal Broken Bones
Robert Haddon is director of the Center for Nanoscale Science and Engineering at the University of California at Riverside. View Slideshow Human bones can shatter in accidents, or they can disintegrate when ravaged by disease and time. But scientists may have a new weapon in the battle against forces that damage the human skeleton.
Carbon nanotubes, incredibly strong molecules just billionths of a meter wide, can function as scaffolds for bone regrowth, according to researchers led by Robert Haddon at the University of California at Riverside. They have found a way to create a stronger and safer frame than the artificial bone scaffolds currently in use.
Human bones are both organic and inorganic. The organic part is made of collagen, the most abundant protein in mammals. The inorganic component is hydroxyapatite, a type of calcium crystal. The collagen forms a sort of natural scaffold over which the calcium crystals organize into bone. The idea in Haddon's research is to use the nanotubes as substitutes for the collagen to promote new bone growth when bones have been broken or worn down.
Haddon and his team chemically treated carbon nanotubes to attract hydroxyapatite in work they published in the June 14 issue of Chemistry of Materials.
"This is nice work," said James Mitchell Tour, a chemistry professor at Rice University. "Anything you can do to take care of people's bones by augmenting the mineralization process is a big deal. It's really nice to see nanotubes being used to function like that."
Carbon nanotubes are an excellent choice for supporting bone, scientists say, because at the molecular scale they are the strongest human-made fiber in existence.
"The advantage of the carbon nanotube here is that at the molecular scale, it is the strongest fiber man will ever make," said Michael Strano, an assistant professor of chemical and biomolecular engineering at the University of Illinois at Urbana-Champaign. "The chemical bonds (in carbon nanotubes) are nature's strongest. Man cannot envision a molecule that will be stronger along its length."
Strano, an expert in carbon nanotube materials. believes the importance of the work stretches beyond bone scaffolds. Though the nanotubes were treated in this case to attract a mineral that might help grow and repair bones, Strano was excited by the possibility of treating the nanotubes in other ways so that they attract, grow and direct all sorts of minerals.
Haddon agreed that his team's biggest accomplishment was discovering how to get the carbon nanotubes to encourage the crystal calcium growth. "Pristine carbon nanotubes can not effectively serve as the nucleus for the growth of hydroxyapatite," he said. "When we tailored the properties of the nanotubes through chemistry, we were able to grow the hydroxyapatite. This result reinforces our belief that, for many applications, nanotube properties have to be tailored through chemistry."
Haddon hopes soon to test how the human body will respond to carbon nanotubes. Even though humans are carbon-based, that's not an iron-clad guarantee that the two will get along smoothly.
Other major questions need to be answered as well. The nanotube solution would likely be injected as a liquid at the site of bone trauma or degradation. Researchers aren't sure if it will know how to organize itself and facilitate growth of the right amount of bone in the right place. It's also possible the nanotube-enhanced bone could be too strong for the surrounding bones and damage the un-enhanced bones, similar to the way a diamond rubbing against copper would eventually degrade the copper.
Nanotube researchers tend to be engineers and material chemists, not experts in tissue engineering. So collaboration between the chemists and bioengineering experts is essential. Tour has established such a partnership with Antonios Mikos, a bioengineering professor at Rice. Together they are researching ways to use nanotubes to strengthen the artificial polymer scaffolds currently in use to repair shattered bones. Tour said they have found that a polymer scaffold composed of just 0.1 percent nanotubes (by weight) has roughly double the structural integrity of a polymer alone.
"Nanotubes are already a big deal in the rubber and elastomer industries," Tour said. "It's going to be a big deal in the medical industry. When we talk about enhancing rigidity in the medical field, one immediately thinks of bones. That's a good place to start."
Carbon nanotubes, incredibly strong molecules just billionths of a meter wide, can function as scaffolds for bone regrowth, according to researchers led by Robert Haddon at the University of California at Riverside. They have found a way to create a stronger and safer frame than the artificial bone scaffolds currently in use.
Human bones are both organic and inorganic. The organic part is made of collagen, the most abundant protein in mammals. The inorganic component is hydroxyapatite, a type of calcium crystal. The collagen forms a sort of natural scaffold over which the calcium crystals organize into bone. The idea in Haddon's research is to use the nanotubes as substitutes for the collagen to promote new bone growth when bones have been broken or worn down.
Haddon and his team chemically treated carbon nanotubes to attract hydroxyapatite in work they published in the June 14 issue of Chemistry of Materials.
"This is nice work," said James Mitchell Tour, a chemistry professor at Rice University. "Anything you can do to take care of people's bones by augmenting the mineralization process is a big deal. It's really nice to see nanotubes being used to function like that."
Carbon nanotubes are an excellent choice for supporting bone, scientists say, because at the molecular scale they are the strongest human-made fiber in existence.
"The advantage of the carbon nanotube here is that at the molecular scale, it is the strongest fiber man will ever make," said Michael Strano, an assistant professor of chemical and biomolecular engineering at the University of Illinois at Urbana-Champaign. "The chemical bonds (in carbon nanotubes) are nature's strongest. Man cannot envision a molecule that will be stronger along its length."
Strano, an expert in carbon nanotube materials. believes the importance of the work stretches beyond bone scaffolds. Though the nanotubes were treated in this case to attract a mineral that might help grow and repair bones, Strano was excited by the possibility of treating the nanotubes in other ways so that they attract, grow and direct all sorts of minerals.
Haddon agreed that his team's biggest accomplishment was discovering how to get the carbon nanotubes to encourage the crystal calcium growth. "Pristine carbon nanotubes can not effectively serve as the nucleus for the growth of hydroxyapatite," he said. "When we tailored the properties of the nanotubes through chemistry, we were able to grow the hydroxyapatite. This result reinforces our belief that, for many applications, nanotube properties have to be tailored through chemistry."
Haddon hopes soon to test how the human body will respond to carbon nanotubes. Even though humans are carbon-based, that's not an iron-clad guarantee that the two will get along smoothly.
Other major questions need to be answered as well. The nanotube solution would likely be injected as a liquid at the site of bone trauma or degradation. Researchers aren't sure if it will know how to organize itself and facilitate growth of the right amount of bone in the right place. It's also possible the nanotube-enhanced bone could be too strong for the surrounding bones and damage the un-enhanced bones, similar to the way a diamond rubbing against copper would eventually degrade the copper.
Nanotube researchers tend to be engineers and material chemists, not experts in tissue engineering. So collaboration between the chemists and bioengineering experts is essential. Tour has established such a partnership with Antonios Mikos, a bioengineering professor at Rice. Together they are researching ways to use nanotubes to strengthen the artificial polymer scaffolds currently in use to repair shattered bones. Tour said they have found that a polymer scaffold composed of just 0.1 percent nanotubes (by weight) has roughly double the structural integrity of a polymer alone.
"Nanotubes are already a big deal in the rubber and elastomer industries," Tour said. "It's going to be a big deal in the medical industry. When we talk about enhancing rigidity in the medical field, one immediately thinks of bones. That's a good place to start."
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