Epigenetic Silencing of Recombinant Adeno-associated Virus Genomes by NP220 and the HUSH Complex
Anshuman Das, Madhuvanthi Vijayan, Eric M. Walton, V. Grace Stafford, David N. Fiflis, Aravind Asokan
Abstract
Recombinant AAV vectors can enable long-term gene expression in a wide variety of tissues. However, transgene silencing has been reported in some human gene therapy clinical trials. Here, we demonstrate the HUSH complex can suppress transcript formation from rAAV vector genomes by epigenetic modification of associated host histones. Further, the AAV capsid appears to play an important role in this pathway. We postulate that modulation of epigenetic pathways could help improve rAAV expression.
Topics & Concepts
BiologyAdeno-associated virusRecombinant DNAEpigeneticsGene silencingVirologyGenomeVirusGeneticsCell biologyGeneVector (molecular biology)Virus-based gene therapy researchCRISPR and Genetic EngineeringRNA Interference and Gene Delivery