Researchers developed a gene editing strategy to repair parts of the DNA affected by microduplications. These small segments of DNA, when copied or duplicated, can ultimately lead to loss of function of the protein and over 100 different rare diseases.
Many gene editing techniques that use CRISPR/Cas9 as an approach take advantage of a DNA repair mechanism called the homology-directed repair pathway, which researchers say is inefficient and known for technical challenges. Instead, researchers used the microhomology-mediated end joining (MMEJ) pathway to remove duplicated sequences and restore the gene’s functional sequence.
Researchers validated the approach in stem cells that can self-replicate from a patient with limb-girdle muscular dystrophy type 2G. This disease is one of eight genetically distinct forms of the disease that affects causes muscle weakness closest to the body’s midline. The team saw that the MMEJ repair mechanism deleted one copy of the microduplication, stitching the DNA back together with high efficiency.
The study, partly funded by NHLBI, appeared in Nature.