Systemic and Persistent Muscle Gene Expression in Rhesus Monkeys with a Liver De-Targeted Adeno-Associated Virus Vector.

Journal Article (Journal Article)

The liver is a major off-target organ in gene therapy approaches for cardiac and musculoskeletal disorders. Intravenous administration of most of the naturally occurring adeno-associated virus (AAV) strains invariably results in vector genome sequestration within the liver. In the current study, we compared the muscle tropism and transduction efficiency of a liver de-targeted AAV variant to AAV9 following systemic administration in newborn rhesus monkeys. In vivo bioluminescence imaging was performed to monitor transgene expression (firefly luciferase) post administration. Results indicated comparable and sustained levels of systemic firefly luciferase gene expression in skeletal muscle over a period of two years. Quantitation of vector biodistribution in harvested tissues post-administration revealed widespread recovery of vector genomes delivered by AAV9 but markedly decreased levels in major systemic organs from the AAV variant. These studies validate the translational potential and safety of liver de-targeted AAV strains for gene therapy of muscle-related diseases.

Full Text

Duke Authors

Cited Authors

  • Tarantal, AF; Lee, CCI; Martinez, ML; Asokan, A; Samulski, RJ

Published Date

  • May 2017

Published In

Volume / Issue

  • 28 / 5

Start / End Page

  • 385 - 391

PubMed ID

  • 28125921

Pubmed Central ID

  • PMC5444483

Electronic International Standard Serial Number (EISSN)

  • 1557-7422

Digital Object Identifier (DOI)

  • 10.1089/hum.2016.130


  • eng

Conference Location

  • United States