Drug Designing: Open Access
Open Access

Intranasal and intraperitoneal adeno-associated virus based formulations for cancer gene therapy applications

9^th Annual Congress on Drug Design & Drug Formulation

October 19-20, 2017 Seoul, South Korea

Maciej Malecki, Milena Czajka, Krzysztof and Gawrychowski

Medical University of Warsaw, Poland

Scientific Tracks Abstracts: Drug Des

Abstract :

Introduction: Melanoma is a cutaneous cancer characterized by the highest mortality rates and a malignancy with the highest potential of dissemination. The prognosis of patients with metastatic melanoma is poor. Treatment proposed so far has not produced beneficial effects. Therefore, one of the current therapeutic approaches to melanoma is gene therapy with the use of recombinant adeno-associated viruses (rAAV) as gene vectors. The rAAV vectors are the principal candidates for virusbased gene therapy because of their small size, broad tissue tropism, safety profile and low immunogenicity. The purpose of this study involved a targeted delivery of rAAV 2/2 and 2/6 formulations to melanoma cells metastasized into murine lungs. Methodology: In our experiments, we used intranasal (in) and intraperitoneal rAAV (ip) formulations of serotype 2/2 and 2/6 encoding Gfp reporter under the control of cmv promoter. The experiments were performed in vivo on B16-F10 melanoma tumor-bearing C57BL/6 mice. The mice were injected with B16-F10 tumor cells via the tail vein. After 14 days the rAAV vectors were administered to the mice by in or ip injection, and 7 days later the mice were euthanized, and the infected tissues collected for further tests. The infection efficiency of melanoma cells metastasized into murine lungs was assessed with qPCR method. At the same time, we performed the analysis of the bio-distribution of rAAV vectors to different organs in mice. Conclusion: The study demonstrated the usefulness of rAAV formulations in introducing genes into metastatic melanoma cells. The highest infection efficiency was observed for serotype 2 after intraperitoneal injection. Gene therapy with the use of rAAV formulations may be a promising therapeutic strategy for melanoma and lung cancer in the future. This work was supported by a grant from NCBiR (Strategmed1/233264/4/NCBR/2014, MentorEYE). Recent Publications 1.Santry LA, Ingrao JC, Yu DL, de Jong JG, van Lieshout LP, Wood GA, Wootton SK (2017) AAV vector distribution in the mouse respiratory tract following four different methods of administration. BMC Biotechnology 17:43-54. 2.Kurosaki F1, Uchibori R1, Mato N, Sehara Y, Saga Y1, Urabe M, Mizukami H, Sugiyama Y, Kume A (2017) Optimization of adeno-associated virus vector-mediated gene transfer to the respiratory tract. Gene Ther. 24: 290-297. 3.Santiago-Ortiz JL, Schaffer DV (2016) Adeno-associated virus (AAV) vectors in cancer gene therapy. J Control Release 28: 287-301. 4.Grecka E, Statkiewicz M, Gorska A, Biernacka M, Grygorowicz MA, Masnyk M, Chmielewski M, Gawarecka K, Chojnacki T, Swiezewska E, Malecki M (2016) Prenyl Ammonium Salts - New Carriers for Gene Delivery: A B16-F10 Mouse Melanoma Model. PLoS One 11:e0153633. 5.Skubis-Zegad�?�?o J, Stachurska A, Malecki M (2013) Vectorology of adeno-associated viruses (AAV). Developmental Period Medicine 17: 202-6.

Biography :

Maciej Malecki, PhD, Prof, is working at the Department of Applied Pharmacy in the Medical University of Warsaw, Poland. He is the author of about 100 publications in the field of medical biology and pharmacy. He is interested in cancer gene therapy and rAAV vectorology.