Ex vivo transduction of microvascular free flaps for localized peptide delivery.
Gene therapy is a promising modality for the treatment of soft tissue malignancies. Our laboratory has developed a novel technique of gene transfer using microvascular free flaps that addresses many of the current barriers preventing gene therapy from achieving widespread clinical use. Our previous work has demonstrated our ability to transduce free flaps with an adenovirus encoding the reporter gene lacZ. In this current study, we show that microvascular free flaps can be transduced with an adenovirus encoding the angiogenesis inhibitor endostatin with high levels of local flap expression. These transduced free flaps were able to serve as "biologic pumps" and were able to secrete endostatin into the serum as demonstrated by enzyme-linked immunosorbent assay. This form of "biologic brachytherapy" could provide a novel approach for the continuous delivery of therapeutic genes to a localized area while avoiding many of the practical obstacles currently limiting gene therapy.
Michaels
Joseph
J
Laboratory of Microvascular Research and Vascular Tissue Engineering, New York University Medical Center, New York, NY 10016, USA.
Dobryansky
Michael
M
Galiano
Robert D
RD
Ceradini
Daniel J
DJ
Bonillas
Robert
R
Jones
Deirdre
D
Seiser
Natalie
N
Levine
Jamie P
JP
Gurtner
Geoffrey C
GC
D000256:Adenoviridae; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D016503:Drug Delivery Systems; D043169:Endostatins / Q000008:administration & dosage*; D004797:Enzyme-Linked Immunosorbent Assay; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors; D015151:Immunoblotting; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012983:Soft Tissue Neoplasms / Q000188:drug therapy*; D013524:Surgical Flaps / Q000098:blood supply*
D020533:Angiogenesis Inhibitors; D043169:Endostatins