Bilamellar cationic liposomes protect adenovectors from preexisting humoral immune responses.
Adenoviral vectors have been widely used for gene therapy, but they are limited both by the presence of a humoral immune response that dramatically decreases the level of transduction after reinjection and by their requirement for target cells to express appropriate receptors such as Coxsackie adenovirus receptor (CAR). To overcome both limits, we encapsulated adenovectors using bilamellar DOTAP:chol liposomes. Electron micrography (EM) showed that these liposomes efficiently encapsulated the vectors, allowing CAR-independent adenovector transduction of otherwise resistant cells. DOTAP:chol-encapsulated adenovectors encoding LacZ or alpha(1)-antitrypsin inhibitor (AAT) were also functionally resistant ex vivo and in vivo to the neutralizing effects of human anti-adenoviral antibodies, unlike other liposomal systems. Hence, bilamellar DOTAP:chol liposomes may be useful for applications using adenovectors in which the target cells lack adenoviral receptors or in which the recipient already has or develops a neutralizing antibody response that would otherwise inactivate readministered vector.
Yotnda
Patricia
P
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas 77030, USA. pyotnda@bcm.tmc.edu
Chen
Dong-Hua
DH
Chiu
Wah
W
Piedra
Pedro A
PA
Davis
Alan
A
Templeton
Nancy Smyth
NS
Brenner
Malcolm K
MK
D000256:Adenoviridae / Q000276:immunology; D000818:Animals; D000917:Antibody Formation; D004337:Drug Carriers; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000276:immunology; D006801:Humans; D008081:Liposomes; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron
D004337:Drug Carriers; D008081:Liposomes