Bioengineered Viral Platform for Intramuscular Passive Vaccine Delivery to Human Skeletal Muscle.

ABSTRACT: Skeletal muscle is ideal for passive vaccine administration as it is easily accessible by intramuscular injection. Recombinant adeno-associated virus (rAAV) vectors are in consideration for passive vaccination clinical trials for HIV and influenza. However, greater human skeletal muscle transduction is needed for therapeutic efficacy than is possible with existing serotypes. To bioengineer capsids with therapeutic levels of transduction, we utilized a directed evolution approach to screen libraries of shuffled AAV capsids in pools of surgically resected human skeletal muscle cells from five patients. Six rounds of evolution were performed in various muscle cell types, and evolved variants were validated against existing muscle-tropic serotypes rAAV1, 6, and 8. We found that evolved variant

SUBMITTER: Paulk NK 

PROVIDER: S-EPMC6077147 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature