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Publication : Exosome-mediated delivery of RNA and DNA for gene therapy.

First Author  Munagala R Year  2021
Journal  Cancer Lett Volume  505
Pages  58-72 PubMed ID  33610731
Mgi Jnum  J:303946 Mgi Id  MGI:6514641
Doi  10.1016/j.canlet.2021.02.011 Citation  Munagala R, et al. (2021) Exosome-mediated delivery of RNA and DNA for gene therapy. Cancer Lett 505:58-72
abstractText  Gene therapy promises to revolutionize biomedicine and personalized medicine by modulating or compensating the expression of abnormal genes. The biggest obstacle for clinical application is the lack of an effective, non-immunogenic delivery system. We show that bovine colostrum exosomes and polyethyleneimine matrix (EPM) delivers short interfering RNA (siRNA) or plasmid DNA (pDNA) for effective gene therapy. KRAS, a therapeutic focus for many cancers, was targeted by EPM-delivered KRAS siRNA (siKRAS) and inhibited lung tumor growth (>70%) and reduced KRAS expression (50%-80%). Aberrant p53 is another therapeutic focus for many cancers. EPM-mediated introduction of wild-type (WT) p53 pDNA (pcDNA-p53) resulted in p53 expression in p53-null H1299 cells in culture, subcutaneous lung tumor, and tissues of p53-knockout mice. Additionally, chemo-sensitizing effects of paclitaxel were restored by exogenous WT p53 in lung cancer cells. Together, this novel EPM technology represents an effective 'platform' for delivery of therapeutic nucleic acids to treat human disease.
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