A promoterless AAV6.2FF-based lung gene editing platform for the correction of surfactant protein B deficiency.

ABSTRACT: Surfactant protein B (SP-B) deficiency is a rare genetic disease that causes fatal respiratory failure within the first year of life. Currently, the only corrective treatment is lung transplantation. Here, we co-transduced the murine lung with adeno-associated virus 6.2FF (AAV6.2FF) vectors encoding a SaCas9-guide RNA nuclease or donor template to mediate insertion of promoterless reporter genes or the (murine) Sftpb gene in frame with the endogenous surfactant protein C (SP-C) gene, without disrupting SP-C expression. Intranasal administration of 3 × 10¹¹ vg donor template and 1 × 10¹¹ vg nuclease consistently edited approximately 6% of lung epithelial cells. Frequency of gene insertion increased in a dose-dependent manner, reaching 20%-25% editing efficiency with th

SUBMITTER: Thomas SP 

PROVIDER: S-EPMC10727957 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature