Researchers at USC and Sangamo Biosciences have developed a more efficient genome editing method for HSPCs.
Gene therapy using hematopoietic stem and progenitor cells (HSPCs) has great potential for treating HIV and other diseases of the blood and immune system. One application of gene therapy that is close to clinical translation is the disruption of the HIV-1 co-receptor, CCR5, to engineer cells that are resistant to HIV infection. While promising, the genome editing process isn’t perfect, so only some of the cells end up carrying the desired modification. HSPCs are relatively rare populations that are quiescent, which makes it difficult to transfer genes into these cells with high efficiency. In addition, correction of a mutation or insertion of new DNA sequences at a specific location is often challenging.
Recently, researchers at University of Southern California reported genome editing in HSPCs with efficiency rates ranging from 17-43% . In collaboration with a team at Sangamo Biosciences, they used zinc finger nucleases (ZFNs) to cut the cell’s DNA at a precise sequence. They found that delivering the ZFNs as mRNAs allowed the DNA cutting and repair process to occur without disruption of the cells. To provide the cells with the ZFN mRNA and new DNA template, they used adeno-associated virus serotype 6 vectors, which are known to naturally enter HSPCs. This strategy achieved site-specific insertion in mobilized peripheral blood CD34+ HSPCs and fetal liver HSPCs at frequencies of 17-43%, which is a new breakthrough for the field. Interestingly, they modified the CD34+CD133+CD90+ cell population, a small component of CD34+ cells known to contain the long-term repopulating hematopoietic stem cells. The genome-edited HSPCs engrafted immune-deficient mice long-term, further confirming the effectiveness of this approach.
The findings of this study will allow robust application of genome-editing technologies in HSPCs, and significantly advance the treatment of diseases of the blood and immune system. HemaCare is a leading provider of a variety of HSPCs for your research purposes.
 Wang, J. et al. Homology-driven genome editing in hematopoietic stem and progenitor cells using ZFN mRNA and AAV6 donors. Nature biotechnology 33, 1256-1263, doi:10.1038/nbt.3408 (2015).