Adeno-associated virus serotype 8 efficiently delivers genes to muscle and heart
Top Cited Papers
- 27 February 2005
- journal article
- research article
- Published by Springer Nature in Nature Biotechnology
- Vol. 23 (3) , 321-328
- https://doi.org/10.1038/nbt1073
Abstract
Systemic gene delivery into muscle has been a major challenge for muscular dystrophy gene therapy, with capillary blood vessels posing the principle barrier and limiting vector dissemination. Previous efforts to deliver genes into multiple muscles have relied on isolated vessel perfusion or pharmacological interventions to enforce broad vector distribution. We compared the efficiency of multiple adeno-associated virus (AAV) vectors after a single injection via intraperitoneal or intravenous routes without additional intervention. We show that AAV8 is the most efficient vector for crossing the blood vessel barrier to attain systemic gene transfer in both skeletal and cardiac muscles of mice and hamsters. Serotypes such as AAV1 and AAV6, which demonstrate robust infection in skeletal muscle cells, were less effective in crossing the blood vessel barrier. Gene expression persisted in muscle and heart, but diminished in tissues undergoing rapid cell division, such as neonatal liver. This technology should prove useful for muscle-directed systemic gene therapy.Keywords
This publication has 53 references indexed in Scilit:
- Regional intravascular delivery of AAV-2-F.IX to skeletal muscle achieves long-term correction of hemophilia B in a large animal modelBlood, 2005
- A Facile Nonviral Method for Delivering Genes and siRNAs to Skeletal Muscle of Mammalian LimbsMolecular Therapy, 2004
- Cross-Dressing the Virion: the Transcapsidation of Adeno-Associated Virus Serotypes Functionally Defines SubgroupsJournal of Virology, 2004
- Efficient and long-term intracardiac gene transfer in δ-sarcoglycan-deficiency hamster by adeno-associated virus-2 vectorsGene Therapy, 2003
- Delivery ofα- andβ-Sarcoglycan by Recombinant Adeno-Associated Virus: Efficient Rescue of Muscle, but Differential ToxicityHuman Gene Therapy, 2002
- Insertional Mutagenesis of the Adeno-Associated Virus Type 2 (AAV2) Capsid Gene and Generation of AAV2 Vectors Targeted to Alternative Cell-Surface ReceptorsHuman Gene Therapy, 2001
- Adeno-Associated Virus Serotype 4 (AAV4) and AAV5 Both Require Sialic Acid Binding for Hemagglutination and Efficient Transduction but Differ in Sialic Acid Linkage SpecificityJournal of Virology, 2001
- CMV-β-Actin Promoter Directs Higher Expression from an Adeno-Associated Viral Vector in the Liver than the Cytomegalovirus or Elongation Factor 1α Promoter and Results in Therapeutic Levels of Human Factor X in MiceHuman Gene Therapy, 2001
- Rescue of Skeletal Muscles of γ-Sarcoglycan- Deficient Mice with Adeno-Associated Virus-Mediated Gene TransferMolecular Therapy, 2000
- rAAV vector-mediated sarcogylcan gene transfer in a hamster model for limb girdle muscular dystrophyGene Therapy, 1999