Prenyl Ammonium Salts--New Carriers for Gene Delivery: A B16-F10 Mouse Melanoma Model

异戊烯基铵盐——基因传递的新载体:B16-F10 小鼠黑色素瘤模型

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作者:Emilia Grecka, Malgorzata Statkiewicz, Agnieszka Gorska, Marzena Biernacka, Monika Anna Grygorowicz, Marek Masnyk, Marek Chmielewski, Katarzyna Gawarecka, Tadeusz Chojnacki, Ewa Swiezewska, Maciej Malecki

Conclusion

Obtained results indicate that APs have a potential as non-viral vectors for cell transfection.

Methods

AP-7, -8, -11 and -15 (aminoprenols composed of 7, 8, 11 or 15 isoprene units, respectively) were examined for their capacity to form complexes with pDNA, for cytotoxicity and ability to transfect genes to cells.

Purpose

Prenyl ammonium iodides (Amino-Prenols, APs), semi-synthetic polyprenol derivatives were studied as prospective novel gene transfer agents.

Results

All the carriers were able to complex DNA. The highest, comparable to commercial reagents, transfection efficiency was observed for AP-15. Simultaneously, AP-15 exhibited the lowest negative impact on cell viability and proliferation--considerably lower than that of commercial agents. AP-15/DOPE complexes were also efficient to introduce pDNA to cells, without much effect on cell viability. Transfection with AP-15/DOPE complexes influenced the expression of a very few among 44 tested genes involved in cellular lipid metabolism. Furthermore, complexes containing AP-15 and therapeutic plasmid, encoding the TIMP metallopeptidase inhibitor 2 (TIMP2), introduced the TIMP2 gene with high efficiency to B16-F10 melanoma cells but not to B16-F10 melanoma tumors in C57BL/6 mice, as confirmed by TIMP2 protein level determination.

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