GENETIC MODIFICATION EFFICIENCY INCREASED TWENTYFOLD
By BRADLEY J. FIKES - bfikes@nctimes.com | Posted: Thursday, January 7, 2010
UC San Diego scientists have made a dramatic advance in creating genetically modified embryonic stem cells suitable for disease research.
The new approach produces embryonic stem cells that contain the disease genes 20 percent of the time, said Yang Xu, a UCSD professor of biology who led the study. Standard methods work less than 1 percent of the time, said Xu, assisted by postdoctoral fellows Hoseok Song and Sun-Ku Chung.
The research was published Thursday in the journal Cell Stem Cell.
Some genetic diseases can't be studied adequately in animals, Xu said, so the ability to produce human cells with the diseases will be of great help. For example, drugs to treat the diseases can be tested in the genetically modified cells, he said.
For the study, researchers transferred disease genes into embryonic stem cells by using "bacterial artificial chromosomes," circular pieces of DNA that resemble the DNA found in bacteria. The structure of these chromosomes make them more likely to introduce the genes into the cell nucleus than with standard methods, Xu said.
California's multibillion-dollar stem cell research program, the California Institute for Regenerative Medicine, funded the work. Neurodegenerative ailments such as Alzheimer's, Parkinson's and Huntington's diseases are among those researchers hope to treat.
Embryonic stem cells are the "ancestral" cells, found in days-old embryos, that turn into nearly all the cells in the body. Researchers hope to turn these cells into those of the type affected by the target disease, such as brain and nerve cells for examining neurodegenerative diseases.
The group used its technology with two disease-related genes. One is p53, which when defective increases the risk of many kinds of cancers. About half of all cancers are believed to involve a defective p53 gene.
The other is called ATM, which when defective causes Ataxia-telangiectasia, a disease that increases the risk of cancer, causes degeneration of certain types of brain cells and degrades telomeres, the protective caps on the ends of chromosomes. When telomeres fray, genes near the ends of chromosomes can become damaged.
Mice are not a good model to study ATM, because their telomeres are much longer than those in humans, Xu said.
"They have huge telomeres, so you can't really study how they get short," Xu said. "They're five to 10 times longer than in humans."
The bacterial artificial chromosome technology should also work on so-called "induced pluripotent stem cells," or IPS cells, Xu said. These are cells, such as those taken from skin, that have been genetically reprogrammed to regress to resemble embryonic stem cells. They are considered more acceptable by those who object to research with embryonic stem cells because human embryos are killed to get the cells.
However, these IPS cells can become genetically instable and develop abnormalities, Xu said, so they are flawed as a tool for understanding diseases.
During the "reprogramming" of these cells, certain tumor-suppressing genes are inactivated, leaving them vulnerable to developing tumors, Xu said.
Researchers are now attempting to develop ways of producing IPS cells that don't have this instability.
IPS cells have the advantage over embryonic stem cells for studying diseases caused by many genetic defects, such as Alzheimer's, Xu said. These cells can be created directly from a patient with the disease. For diseases where the genetic cause is simple, embryonic stem cells are superior.
Call staff writer Bradley J. Fikes at 760-739-6641. Read his blogs at bizblogs.nctimes.com.
By BRADLEY J. FIKES - bfikes@nctimes.com | Posted: Thursday, January 7, 2010
UC San Diego scientists have made a dramatic advance in creating genetically modified embryonic stem cells suitable for disease research.
The new approach produces embryonic stem cells that contain the disease genes 20 percent of the time, said Yang Xu, a UCSD professor of biology who led the study. Standard methods work less than 1 percent of the time, said Xu, assisted by postdoctoral fellows Hoseok Song and Sun-Ku Chung.
The research was published Thursday in the journal Cell Stem Cell.
Some genetic diseases can't be studied adequately in animals, Xu said, so the ability to produce human cells with the diseases will be of great help. For example, drugs to treat the diseases can be tested in the genetically modified cells, he said.
For the study, researchers transferred disease genes into embryonic stem cells by using "bacterial artificial chromosomes," circular pieces of DNA that resemble the DNA found in bacteria. The structure of these chromosomes make them more likely to introduce the genes into the cell nucleus than with standard methods, Xu said.
California's multibillion-dollar stem cell research program, the California Institute for Regenerative Medicine, funded the work. Neurodegenerative ailments such as Alzheimer's, Parkinson's and Huntington's diseases are among those researchers hope to treat.
Embryonic stem cells are the "ancestral" cells, found in days-old embryos, that turn into nearly all the cells in the body. Researchers hope to turn these cells into those of the type affected by the target disease, such as brain and nerve cells for examining neurodegenerative diseases.
The group used its technology with two disease-related genes. One is p53, which when defective increases the risk of many kinds of cancers. About half of all cancers are believed to involve a defective p53 gene.
The other is called ATM, which when defective causes Ataxia-telangiectasia, a disease that increases the risk of cancer, causes degeneration of certain types of brain cells and degrades telomeres, the protective caps on the ends of chromosomes. When telomeres fray, genes near the ends of chromosomes can become damaged.
Mice are not a good model to study ATM, because their telomeres are much longer than those in humans, Xu said.
"They have huge telomeres, so you can't really study how they get short," Xu said. "They're five to 10 times longer than in humans."
The bacterial artificial chromosome technology should also work on so-called "induced pluripotent stem cells," or IPS cells, Xu said. These are cells, such as those taken from skin, that have been genetically reprogrammed to regress to resemble embryonic stem cells. They are considered more acceptable by those who object to research with embryonic stem cells because human embryos are killed to get the cells.
However, these IPS cells can become genetically instable and develop abnormalities, Xu said, so they are flawed as a tool for understanding diseases.
During the "reprogramming" of these cells, certain tumor-suppressing genes are inactivated, leaving them vulnerable to developing tumors, Xu said.
Researchers are now attempting to develop ways of producing IPS cells that don't have this instability.
IPS cells have the advantage over embryonic stem cells for studying diseases caused by many genetic defects, such as Alzheimer's, Xu said. These cells can be created directly from a patient with the disease. For diseases where the genetic cause is simple, embryonic stem cells are superior.
Call staff writer Bradley J. Fikes at 760-739-6641. Read his blogs at bizblogs.nctimes.com.