Epigenetic Silencing of Recombinant Adeno-associated Virus Genomes by NP220 and the HUSH Complex

• Published in: Journal of virology Vol. 96; no. 4; p. e0203921
• Main Authors: Das, Anshuman, Vijayan, Madhuvanthi, Walton, Eric M., Stafford, V. Grace, Fiflis, David N., Asokan, Aravind
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 23.02.2022
• Subjects: Antigens, Neoplasm - genetics; Antigens, Neoplasm - metabolism; Capsid - metabolism; Dependovirus - genetics; Dependovirus - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Epigenesis, Genetic; Gene Silencing; Genome, Viral - genetics; HEK293 Cells; Humans; Multiprotein Complexes - genetics; Multiprotein Complexes - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Phosphoproteins - genetics; Phosphoproteins - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Serogroup; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic; Transgenes - genetics; Virology; Virus-Cell Interactions; gene silencing; gene therapy; virus-host interactions; AAV; DNA damage

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 modific...