title: The potential of adeno-associated viral vectors for gene delivery to muscle tissue.
abstract: BACKGROUND
  Muscle-directed gene therapy is rapidly gaining attention primarily because muscle is an easily accessible target tissue and is also associated with various severe genetic disorders. Localized and systemic delivery of recombinant adeno-associated virus (rAAV) vectors of several serotypes results in very efficient transduction of skeletal and cardiac muscles, which has been achieved in both small and large animals, as well as in humans. Muscle is the target tissue in gene therapy for many muscular dystrophy diseases, and may also be exploited as a biofactory to produce secretory factors for systemic disorders. Current limitations of using rAAVs for muscle gene transfer include vector size restriction, potential safety concerns such as off-target toxicity and the immunological barrier composing of pre-existing neutralizing antibodies and CD8(+) T-cell response against AAV capsid in humans.
  
  
  METHODS
  In this article, we will discuss basic AAV vector biology and its application in muscle-directed gene delivery, as well as potential strategies to overcome the aforementioned limitations of rAAV for further clinical application.
  
  
  CONCLUSIONS
  Delivering therapeutic genes to large muscle mass in humans is arguably the most urgent unmet demand in treating diseases affecting muscle tissues throughout the whole body. Muscle-directed, rAAV-mediated gene transfer for expressing antibodies is a promising strategy to combat deadly infectious diseases. Developing strategies to circumvent the immune response following rAAV administration in humans will facilitate clinical application.
authors.affiliation: University of Massachusetts Medical School, Gene Therapy Center, 368 Plantation Street, AS6-2049, Worcester, MA 01605, USA.|University of Massachusetts Medical School, Department of Microbiology and Physiology Systems, Worcester, MA 01605, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: University of Massachusetts Medical School, Gene Therapy Center, 368 Plantation Street, AS6-2049, Worcester, MA 01605, USA.|University of Massachusetts Medical School, Division of Hematology/Oncology, Department of Pediatrics, Worcester, MA 01605, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zhong
authors.affiliation: University of Massachusetts Medical School, Gene Therapy Center, 368 Plantation Street, AS6-2049, Worcester, MA 01605, USA.|University of Massachusetts Medical School, Department of Microbiology and Physiology Systems, Worcester, MA 01605, USA.
authors.forename: M Abu
authors.initials: MA
authors.lastname: Nahid
authors.affiliation: University of Massachusetts Medical School, Gene Therapy Center, 368 Plantation Street, AS6-2049, Worcester, MA 01605, USA.|University of Massachusetts Medical School, Department of Microbiology and Physiology Systems, Worcester, MA 01605, USA.|Sichuan University, West China Hospital, State Key Laboratory of Biotherapy, Chengdu, Sichuan, People's Republic of China.
authors.forename: Guangping
authors.initials: G
authors.lastname: Gao
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D009132:Muscles / Q000378:metabolism*