Charge-reversal lipids for siRNA transfection

BIOL 183

Sang Yeon Kwon, is5416@gmail.com1, Carla A. H. Prata, cprata@bu.edu2, Dan Luo, dl79@cornell.edu1, and Mark W. Grinstaff, mgrin@bu.edu3. (1) Biological and Environmental Engineering, Cornell University, 220, Riley-Robb Hall, Ithaca, NY 14853, (2) Departments of Biomedical Engineering and Chemistry, Boston University, 590 Commonwealth Ave., Boston, MA 02215, (3) Department of Chemistry, Boston University, 590 Commonwealth Avenue, Boston, MA 02215
RNAi is a relatively new technology that has the potential to treat genetic diseases or to be used along with the traditional drugs to increase their efficacy. This strategy involves the targeted post-transcriptional degradation of the mRNA thereby inhibiting the synthesis of the desired protein. This leads to silencing of the gene expression. The key species involved in this process are short interfering RNA. However, delivery of these macromolecules into cells in vitro or in vivo remains a critical challenge. siRNA is delivered into the cells by physical methods or by using carriers (viral or non-viral vectors). We have developed charge-reversal amphiphiles, which facilitate the escape of nucleic acid from the amphiphile/nucleic acid complex in the cell, and thus improve transfection efficiency. In the presence of nucleic acid a strong complex is formed with the amphiphile. Once in the cell, esterases hydrolyze the terminal ester linkage of the amphiphile affecting overall amphiphile charge from cationic to anionic. This charge reversal effect is proposed for releasing the DNA from the amphiphiles. The delivery of siRNA was performed in several cell lines and enhanced gene knockdown was observed.
 

Frontiers in Chemical Biology
5:00 PM-7:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Biological Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007