Journal
CANCER LETTERS
Volume 505, Issue -, Pages 58-72Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2021.02.011
Keywords
Exosome; Cancer; Delivery; siRNA; Plasmid-DNA
Categories
Funding
- 3P Biotechnologies, Inc., Louisville, KY
- NCI SBIR [R44-CA-221487]
- Agnes Brown Duggan Endowment
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The use of bovine colostrum exosomes and polyethyleneimine matrix for gene delivery shows promise in targeting KRAS and WT p53 for effective gene therapy, representing a novel platform for therapeutic nucleic acids delivery to treat human disease.
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, nonimmunogenic 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, chemosensitizing 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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