Microsphere-liposome complexes protect adenoviral vectors from neutralising antibody without losses in transfection efficiency, in-vitro.
Adenoviral vectors have been commonly used in gene therapy protocols but the success of their use is often limited by the induction of host immunity to the vector. Following exposure to the adenoviral vector, adenoviral-specific neutralising antibodies are produced, which limits further administration. This study examines the effectiveness of a novel combination of microspheres and liposomes for the shielding of adenovirus from neutralising antibodies in an in-vitro setting. We show that liposomes are effective in the protection of adenovirus from neutralising antibody and that the conjugation of these complexes to microspheres augments the level of protection. This study further reveals that previously neutralised adenovirus may still be transported into the cell via liposome-cell interactions and is still capable of expressing its genes, making this vector an effective tool for circumvention of the humoral immune response. We also looked at possible side effects of using the complexes, namely increases in cytotoxicity and reductions in transfection efficiency. Our results showed that varying the liposome:adenovirus ratio can reduce the cytotoxicity of the vector as well as increase the transfection efficiency. In addition, in cell lines that are adenoviral competent, transfection efficiencies on par with uncomplexed adenoviral vectors were achievable with the combination vector.
Steel
Jason C
JC
School of Biomedical Science, Charles Sturt University, P. O. Box 588, Wagga Wagga 2678, Australia. jsteel@csu.edu.au
Cavanagh
Heather M A
HM
Burton
Mark A
MA
Kalle
Wouter H J
WH
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D000917:Antibody Formation; D016923:Cell Death; D016503:Drug Delivery Systems; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes; D008863:Microspheres; D014162:Transfection
D008081:Liposomes