Transductional and transcriptional targeting of cancer cells using genetically engineered viral vectors.
Gene delivery vectors, including adenovirus (Ad) and adeno-associated virus (AAV), are inefficient and non-selective for cancer due to low levels of viral receptors with high levels on other tissues, including liver. We tested Ads and AAVs with the SIGYPLP-targeting peptide inserted into virus capsids for transduction in a panel of cancer cells. Six of twelve lines (C8161, PC-3, G-CCM, MKN-45, LnCAP and A549) were transduced, independently of native viral tropism. Furthermore the candidate cancer gene therapy promoter FLT-1 was active in three of these six cell lines. This offers the potential for dual targeting of selected cancer cells.
Nicklin
Stuart A
SA
Division of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow G11 6NT, UK.
Dishart
Kate L
KL
Buening
Hildegard
H
Reynolds
Paul N
PN
Hallek
Michael
M
Nemerow
Glen R
GR
Von Seggern
Dan J
DJ
Baker
Andrew H
AH
D000256:Adenoviridae / Q000235:genetics*; D000229:Dependovirus / Q000235:genetics*; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D011401:Promoter Regions, Genetic; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D014158:Transcription, Genetic; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011991:Receptors, Virus