Convection-enhanced delivery of AAV-2 combined with heparin increases TK gene transfer in the rat brain.
Adeno-associated virus type2 (AAV-2) binds to heparan-sulfate proteoglycans on the cell surface. In vivo, attachment of viral particles to cells adjacent to the injection tract limits the distribution of AAV-2 when infused into the CNS parenchyma and heparin co-infusion might decrease the binding of AAV-2 particles to cells in the vicinity of the infusion tract. We have previously shown that heparin co-infusion combined with convection enhanced delivery enhances distribution of the GDNF family trophic factors (heparin-binding proteins) in the rat brain. In this work we show that heparin co-infusion significantly increases the volume of distribution of AAV-2 as demonstrated by immunoreactivity to the transgene product 6 days after infusion into the rat striatum.
Nguyen
J B
JB
Molecular Therapeutics Section, National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, MD 20892, USA.
Sanchez-Pernaute
R
R
Cunningham
J
J
Bankiewicz
K S
KS
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D018481:Convection; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D000229:Dependovirus / Q000187:drug effects* / Q000502:physiology; D016503:Drug Delivery Systems; D005260:Female; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000502:physiology; D018014:Gene Transfer Techniques; D017930:Genes, Reporter / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000187:drug effects* / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology*; D007150:Immunohistochemistry; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000821:virology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism
D000925:Anticoagulants; D005904:Glial Fibrillary Acidic Protein; D006493:Heparin; D013937:Thymidine Kinase