Publication: Stem Cells and Development. 25(20): 1591-1603.
Published Date: 2016
Demonstrated ability to induce patient-derived Fanconi Anemia cells to pluripotency for patient-specific therapeutic cell derivation.
During genome engineering, precision sequence alteration is achieved by employing an exogenous DNA molecule (repair template) and programmable nucleases for site-specific, permanent sequence repair that is controlled by endogenous regulatory elements. This differs from more classic gene therapy that utilizes full-length, functional cDNA partnered with viral vectors, which increases the risk of insertional mutagenesis. Disorders like Fanconi anemia (FA) are particularly sensitive to genomic alterations, and are not receptive to curative hematopoietic cell transplants (HCTs). The authors differentiated patient-derived FA cells into induced pluripotent stem (iPS) cells, and then used the CRISPR/Cas9 system to mediate corrections in the Fanconi anemia I gene. It was shown that gene-corrected iPSCs were readily differentiated into hematopoietic stem cells suitable for HCT.