Scientists at Harvard University and the Broad Institute of MIT and Harvard have developed a new class of genome editing tool. This new “base editor” can directly repair the type of single-letter changes in the human genome that account for approximately half of human disease-associated point mutations. These mutations are associated with disorders ranging from genetic blindness to sickle-cell anemia to metabolic disorders to cystic fibrosis.
The research team, led by David Liu, professor of chemistry and chemical biology at Harvard University, core institute member at the Broad Institute, and a Howard Hughes Medical Institute (HHMI) investigator, developed a molecular machine that can convert the DNA base pair A•T to G•C, without cutting the double helix, with high efficiency and virtually no undesired products. The development is an important addition to the growing suite of genome editing tools.
The new system is described in the journal Nature.
In addition to Liu, the study was led by Nicole Gaudelli, a postdoctoral fellow in Liu’s lab; Alexis Komor, a former postdoctoral fellow in Liu’s lab who is now an assistant professor at UCSD; graduate student Holly Rees; former graduate students Michael Packer and Ahmed Badran, and former postdoctoral fellow David Bryson.
The new system, dubbed Adenine Base Editor (ABE), can be programmed to target a specific base pair in a genome using a guide RNA and a modified form of CRISPR-Cas9. It works by rearranging the atoms in a target adenine (A) — one of the four bases that make up DNA — to instead resemble guanine (G), and then tricking cells into fixing the other DNA strand to complete the base pair conversion, making the change permanent. As a result, what used to be an A•T base pair becomes a G•C base pair.
Not only is the system very efficient compared with other genome editing techniques for correcting point mutations, but there are virtually no detectable byproducts such as random insertions, deletions, translocations, or other base-to-base conversions.
Making this specific change is important because approximately half of the 32,000 disease-associated point mutations already identified by researchers are a change from G•C to A•T.
“We developed a new base editor a molecular machine that in a programmable, irreversible, efficient, and clean manner can correct these mutations in the genome of living cells,” said Liu, who is also the Richard Merkin professor and director of the Merkin Institute of Transformative Technologies in Healthcare at the Broad.
Scientists at Harvard University and the Broad Institute of MIT and Harvard have developed a new class of genome editing tool. This new “base editor” can directly repair the type of single-letter changes in the human genome that account for approximately half of human disease-associated point mutations. These mutations are associated with disorders ranging from genetic blindness to sickle-cell anemia to metabolic disorders to cystic fibrosis.
The research team, led by David Liu, professor of chemistry and chemical biology at Harvard University, core institute member at the Broad Institute, and a Howard Hughes Medical Institute (HHMI) investigator, developed a molecular machine that can convert the DNA base pair A•T to G•C, without cutting the double helix, with high efficiency and virtually no undesired products. The development is an important addition to the growing suite of genome editing tools.
The new system is described in the journal Nature.
In addition to Liu, the study was led by Nicole Gaudelli, a postdoctoral fellow in Liu’s lab; Alexis Komor, a former postdoctoral fellow in Liu’s lab who is now an assistant professor at UCSD; graduate student Holly Rees; former graduate students Michael Packer and Ahmed Badran, and former postdoctoral fellow David Bryson.
The new system, dubbed Adenine Base Editor (ABE), can be programmed to target a specific base pair in a genome using a guide RNA and a modified form of CRISPR-Cas9. It works by rearranging the atoms in a target adenine (A) — one of the four bases that make up DNA — to instead resemble guanine (G), and then tricking cells into fixing the other DNA strand to complete the base pair conversion, making the change permanent. As a result, what used to be an A•T base pair becomes a G•C base pair.
Not only is the system very efficient compared with other genome editing techniques for correcting point mutations, but there are virtually no detectable byproducts such as random insertions, deletions, translocations, or other base-to-base conversions.
Making this specific change is important because approximately half of the 32,000 disease-associated point mutations already identified by researchers are a change from G•C to A•T.
“We developed a new base editor a molecular machine that in a programmable, irreversible, efficient, and clean manner can correct these mutations in the genome of living cells,” said Liu, who is also the Richard Merkin professor and director of the Merkin Institute of Transformative Technologies in Healthcare at the Broad.
No comments:
Post a Comment