Scientists demonstrate proof-of-concept for the application of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing as a therapeutic approach to correct gene mutation in patients with alpha-1 antitrypsin deficiency.
Alpha-1 antitrypsin (AAT) deficiency is a genetic condition characterized by low alpha 1 proteinase inhibitor. Reduced levels of AAT results in abnormal degradation of lung tissue, leading to the development of progressive lung disease and emphysema.
Genome editing with the CRISPR-Cas9 tool is revolutionizing the field of genetic engineering. In the present study, researchers at the University of Massachusetts Medical School have investigated whether CRISPR-mediated gene editing in the liver could correct AAT mutation. To do this, the team used adeno-associated viral vector (AAV) to deliver CRISPR into a mice model of AAT deficiency. Co-injecting two AAVs: one expressing Cas9 and the other expressing an AAT guide RNA and homology-dependent repair template in mice partially restored AAT levels in serum and corrected the gene in liver.
Findings from this study published in Human Gene Therapy shows that this strategy of targeted genomic correction could be translated for the treatment of patients with AAT deficiency and could be applicable to the treatment of other genetic diseases.
Source: Song CQ et al., In vivo genome editing partially restores alpha1-antitrypsin in a murine model of AAT deficiency. Human Gene Therapy March 2018. DOI