Spatial genomics of AAVs reveals mechanism of transcriptional crosstalk that enables targeted delivery of large genetic cargo.

Gerard M Coughlin Mate BorsosNathan ApplingBre'Anna H BarcelonaAcacia M H MayfieldElisha D MackeyRana A Eser Xinhong Chen Sripriya Ravindra Kumar Viviana Gradinaru

Published in: bioRxiv : the preprint server for biology (2023)

by AAVs is a generalized phenomenon. Spatial genomics techniques, AAV-Zombie and SpECTr, reveal that AAV genome concatemerization facilitates transcriptional crosstalk.Transcriptional crosstalk can be leveraged for minimally-invasive, targeted AAV delivery of large cargo, including machinery for CRISPR-based gene editing and manipulation.Transcriptional crosstalk enables cell-type specific gene disruption in wildtype animals, recapitulating behavioural phenotypes of genetic knockouts.

Keyphrases

genome wide
gene expression
transcription factor
minimally invasive
dna methylation
copy number
single cell
gene therapy
heat shock
cancer therapy
drug delivery