期刊
PHARMACEUTICS
卷 14, 期 6, 页码 -出版社
MDPI
DOI: 10.3390/pharmaceutics14061271
关键词
cell-penetrating peptide; mRNA; cancer therapy; nucleic acid delivery system
资金
- Ministry of Food and Drug Safety [22203MFDS406]
- Bio & Medical Technology Development Program [NRF-2022M3E5F1018529]
- Intramural Research Program of KIST
In vitro transcribed mRNA has potential in cancer gene therapy and cancer vaccines. Cell-penetrating peptides (CPPs) show promise as gene delivery tools. This study optimized CPP/mRNA complexes and demonstrated their protective effect against RNase, as well as high cellular uptake and protein expression.
In vitro transcribed mRNA for the synthesis of any given protein has shown great potential in cancer gene therapy, especially in cancer vaccines for immunotherapy. To overcome physiological barriers, such as rapid degradation by enzymatic attack and poor cellular uptake due to their large size and hydrophilic properties, many delivery carriers for mRNAs are being investigated for improving the bioavailability of mRNA. Recently, cell-penetrating peptides (CPPs) have received attention as promising tools for gene delivery. In terms of their biocompatibility and the ability to target specific cells with the versatility of peptide sequences, they may provide clues to address the challenges of conventional delivery systems for cancer mRNA delivery. In this study, optimal conditions for the CPP/mRNA complexes were identified in terms of complexation capacity and N/P ratio, and protection against RNase was confirmed. When cancer cells were treated at a concentration of 6.8 nM, which could deliver the highest amount of mRNA without toxicity, the amphipathic CPP/mRNA complexes with a size less than 200 nm showed high cellular uptake and protein expression. With advances in our understanding of CPPs, CPPs designed to target tumor tissues will be promising for use in developing a new class of mRNA delivery vehicles in cancer therapy.
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