Adeno-associated virus serotypes 1 to 5 mediated tumor cell directed gene transfer and improvement of transduction efficiency.

Gene therapy is an attractive new approach for the treatment of cancer. Therefore, the development of efficient vector systems is of crucial importance in this field. Different adeno-associated virus (AAV) serotypes have been characterized so far, which show considerable differences in tissue tropism. Consequently, we aimed to characterize the most efficient serotype for this application. To exclude all influences other than those provided by the capsid, all serotypes contained the same transgene cassette flanked by the AAV2 inverted terminal repeats. We systematically compared these vectors for efficiency in human cancer cell directed gene transfer. In order to identify limiting steps, the influence of second-strand synthesis and proteasomal degradation of AAV in a poorly transducible cell line were examined. AAV2 was the most efficient serotype in all solid tumor cells and primary melanoma cells with transduction rates up to 98 +/- 0.3%. Transduction above 70% could be reached with serotypes 1 (in cervical and prostate carcinoma) and 3 (in cervical, breast, prostate and colon carcinoma) using 1000 genomic particles per cell. In the colon carcinoma cell line HT-29 proteasomal degradation limited AAV1-AAV4-mediated gene transfer. Moreover, inefficient second-strand synthesis prevents AAV2-mediated transgene expression in this cell line. Recent advances in AAV-vector technology suggest that AAV-based vectors can be used for cancer gene therapy. Our comparative analysis revealed that, although AAV2 is the most promising candidate for such an application, serotypes 1 and 3 are valid alternatives. Furthermore, the use of self-complementary AAV vectors and proteasome inhibitors significantly improves cancer cell transduction.

Hacker UT ，Wingenfeld L ，Kofler DM ，Schuhmann NK ，Lutz S ，Herold T ，King SB ，Gerner FM ，Perabo L ，Rabinowitz J ，McCarty DM ，Samulski RJ ，Hallek M ，Büning H ... -  《JOURNAL OF GENE MEDICINE》

Efficacy of recombinant adeno-associated viral vectors serotypes 1, 2, and 5 for the transduction of pancreatic and colon carcinoma cells.

Teschendorf C ，Emons B ，Muzyczka N ，Graeven U ，Schmiegel W ... -  《-》

Adeno-associated virus mediated gene transfer into lung cancer cells promoting CD40 ligand-based immunotherapy.

Wu JQ ，Zhao WH ，Li Y ，Zhu B ，Yin KS ... -  《VIROLOGY》

Adeno-associated virus vectors serotyped with AAV8 capsid are more efficient than AAV-1 or -2 serotypes for widespread gene delivery to the neonatal mouse brain.

Broekman ML ，Comer LA ，Hyman BT ，Sena-Esteves M ... -  《NEUROSCIENCE》

Gene delivery to the vasculature mediated by low-titre adeno-associated virus serotypes 1 and 5.

Sen S ，Conroy S ，Hynes SO ，McMahon J ，O'Doherty A ，Bartlett JS ，Akhtar Y ，Adegbola T ，Connolly CE ，Sultan S ，Barry F ，Katusic ZS ，O'Brien T ... -  《JOURNAL OF GENE MEDICINE》