Corporate Banner
Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

No Extra Mutations in Modified Stem Cells, Study Finds

Published: Saturday, July 12, 2014
Last Updated: Saturday, July 12, 2014
Bookmark and Share
New results ease previous concerns that gene-editing techniques-used to develop therapies for genetic diseases-could add unwanted mutations to stem cells.

The ability to switch out one gene for another in a line of living stem cells has only crossed from science fiction to reality within this decade. As with any new technology, it brings with it both promise-the hope of fixing disease-causing genes in humans, for example-as well as questions and safety concerns.

Now, Salk scientists have put one of those concerns to rest: using gene-editing techniques on stem cells doesn't increase the overall occurrence of mutations in the cells. The new results were published July 3 in the journal Cell Stem Cell.

"The ability to precisely modify the DNA of stem cells has greatly accelerated research on human diseases and cell therapy," says senior author Juan Carlos Izpisua Belmonte, professor in Salk's Gene Expression Laboratory. "To successfully translate this technology into the clinic, we first need to scrutinize the safety of these modified stem cells, such as their genome stability and mutational load."

When scientists want to change the sequence of a stretch of DNA inside cells-either for research purposes or to fix a genetic mutation for therapeutic purposes-they have their choice of two methods. They can use an engineered virus to deliver the new gene to a cell; the cell then integrates the new DNA sequence in place of the old one.

Or scientists can use what's known as custom targeted nucleases, such as TALEN proteins, which cut DNA at any desired location. Researchers can use the proteins to cut a gene they want to replace, then add a new gene to the mix. The cell's natural repair mechanisms will paste the new gene in place.

Previously, Belmonte's lab had pioneered the use of modified viruses, called helper-dependent adenoviral vectors (HDAdVs) to correct the gene mutation that causes sickle cell disease, one of the most severe blood diseases in the world. He and his collaborators used HDAdVs to replace the mutated gene in a line of stem cells with a mutant-free version, creating stem cells that could theoretically be infused into patients' bone marrow so that their bodies create healthy blood cells.

Before such technologies are applied to humans, though, researchers like Belmonte wanted to know whether there were risks of editing the genes in stem cells. Even though both common gene-editing techniques have been shown to be accurate at altering the right stretch of DNA, scientists worried that the process could make the cells more unstable and prone to mutations in unrelated genes-such as those that could cause cancer.

"As cells are being reprogrammed into stem cells, they tend to accumulate many mutations," says Mo Li, a postdoctoral fellow in Belmonte's lab and an author of the new paper. "So people naturally worry that any process you perform with these cells in vitro-including gene editing-might generate even more mutations."

To find out whether this was the case, Belmonte's group, in collaboration with BGI and the Institute of Biophysics, Chinese Academy of Sciences in China, turned to a line of stem cells containing the mutated gene that causes sickle cell disease. They edited the genes of some cells using one of two HDAdV designs, edited others using one of two TALEN proteins, and kept the rest of the cells in culture without editing them. Then, they fully sequenced the entire genome of each cell from the four edits and control experiment.

While all of the cells gained a low level of random gene mutations during the experiments, the cells that had undergone gene-editing-whether through HDAdV-or TALEN-based approaches-had no more mutations than the cells kept in culture.

"We were pleasantly surprised by the results," Keiichiro Suzuki, a postdoctoral fellow in Belmonte's lab and an author of the study, says. "People have found thousands of mutations introduced during iPSC reprogramming. We found less than a hundred single nucleotide variants in all cases."

The finding, Li adds, doesn't necessarily mean that there are no inherent risks to using stem cells with edited genes, but that the editing process doesn't make the stem cells any less safe.

"We concluded that the risk of mutation isn't inherently connected to gene editing," he says. "These cells present the same risks as using any other cells manipulated for cell or gene therapy." He adds that two other papers published in the same issue support their results (one by Johns Hopkins University and one from Harvard University and collaborators).

The Belmonte group is planning more studies to address whether gene-repair in other cell types, using other approaches, or targeting other genes could be more or less likely to cause unwanted mutations. For now, they hope their findings encourage those in the field to keep pursuing gene-editing techniques as a potential way to treat genetic diseases in the future.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,200+ scientific posters on ePosters
  • More than 4,800+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Epigenetic Variations Between Tissues
A Salk Institute-led team has generated a map of the human methylome, gaining insight into patterns of DNA methylation of various tissues.
Wednesday, June 03, 2015
Vital Step in Stem Cell Growth Revealed
Salk scientists' finding could aid regenerative and cancer therapies.
Thursday, May 07, 2015
Gene-Editing Technique Offers Hope For Hereditary Diseases
Salk scientists use molecular "scissors" to eliminate mitochondrial mutations in eggs and embryos.
Monday, April 27, 2015
Cellular Scissors Chop up HIV Virus
Salk scientists re-engineered the bacterial defense system CRISPR to recognize HIV inside human cells and destroy the virus, offering a potential new therapy.
Thursday, March 12, 2015
Salk Institute Receives $3M Gift for Ageing Research
The gift from the Glenn Foundation for Medical Research will allow the Institute to continue conducting research to understand the biology of normal human aging and age-related diseases.
Friday, May 23, 2014
Circadian Clock Gene Linked to Eating Schedule
Research from the Salk Institute has shown that mutations in the circadian genes could drive night eating syndrome.
Friday, May 23, 2014
Salk Institute and Stanford Lead New $40M Stem Cell Genomics Center
Collaborative research center will bridge genomics and stem cell projects to find new therapies.
Sunday, February 02, 2014
Researchers Chart Epigenomics of Stem Cells That Mimic Early Human Development
Collaborative study will help overcome hurdles to using stem cells to treat diseases and injuries.
Friday, May 10, 2013
Salk Institute Awarded Historic $42 Million Grant to Establish Center for Genomic Medicine
World-renowned research facility receives largest single donation in its 53-year history.
Thursday, January 24, 2013
Chromosome "Anchors" Organize DNA during Cell Division
Salk discovery of new role for telomeres in cellular growth may shed light on aging and age-related diseases.
Wednesday, January 09, 2013
Salk Scientists Pinpoint Key Player in Parkinson's Disease Neuron Loss
Stem cell study may help to unravel how a genetic mutation leads to Parkinson's symptoms.
Tuesday, October 23, 2012
Cold Viruses Point the way to New Cancer Therapies
Cold viruses generally get a bad rap, but new findings by a team of scientists at the Salk Institute for Biological Studies suggest that these viruses might also be a valuable ally in the fight against cancer.
Thursday, October 18, 2012
Reprogramming Signature may help Overcome Barriers to Regenerative Medicine
Salk scientists show nine genes at heart of epigenetic changes in induced pluripotent stem cells.
Friday, September 21, 2012
Salk Stem-Cell Research Shows Promise in Sickle-Cell Disease
Salk Stem-Cell Research Shows Promise in Sickle-Cell Disease Researchers are using cells from sickle-cell patients to potentially cure the anemia-inducing condition that affects one in every 12 black Americans. The method developed by Salk researchers also may be used to reverse other disorders linked to the same gene mutation implicated in sickle-cell disease.
Friday, December 09, 2011
Editing Scrambled Genes in Human Stem Cells may Help Realize the Promise of Combined Stem Cell-gene Therapy
Researchers at the Salk Institute successfully edited a diseased gene in patient-specific induced pluripotent stem cells as well as adult stem cells.
Tuesday, May 24, 2011
Scientific News
Liquid Biopsies: Miracle Diagnostic or Next New Fad?
Thanks to the development of highly specific gene-amplification and sequencing technologies liquid biopsies access more biomarkers relevant to more cancers than ever before.
Discovered Through ‘Big Data’ Analysis
Researchers at the SBP have identified over 100 new genetic regions that affect the immune response to cancer.
New Therapeutic Targets For Small Cell Lung Cancer Identified
Researchers at UTSW Medical Center have identified a protein termed ASCL1 that is essential to the development of small cell lung cancer and that, when deleted in the lungs of mice, prevents the cancer from forming.
Deciphering Inactive X Chromosomes
Untangling the Barr body of inactive X chromosomes valuable for understanding chromosome structure and gene expression.
Micro Disease-Detecting Senor Created
Researchers at McMaster University have created a microscopic disease-detecting sensor that can turn on to detect trace amounts of substances.
Liquid Biopsies Treating Ovarian Cancer
Researchers have discovered a promising monitor and treat recurrence of ovarian cancer. Detecting cancer long before tumours reappear.
Uncovering a New Principle in Chemotherapy Resistance in Breast Cancer
The NIH study has revealed an entirely unexpected process for acquiring drug resistance that bypasses the need to re-establish DNA damage repair in breast cancers that have mutant BRCA1 or BRCA2 genes.
Understanding Treatment Resistant Melanoma
Researchers have determined how advanced melanoma becomes resistant; a development toward developing treatments.
Investigating ‘Black Box’ of Human Genetics
Investigations into inactive X chromosomes have shown unusual DNA repeat elements are essential for maintaining 3D structure.
Liquid Biopsies: DNA Size Matters
Study finds circulating tumour DNA can be distinguished from healthy DNA through fragment size identification.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,200+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,800+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!