The Potential of Cell-Penetrating Peptides for mRNA Delivery to Cancer Cells

Yelee Kim, Hyosuk Kim, Eun Hye Kim, Hochung Jang, Yeongji Jang, Sung Gil Chi, Yoosoo Yang, Sun Hwa Kim

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)


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.

Original languageEnglish
Article number1271
Issue number6
Publication statusPublished - 2022 Jun

Bibliographical note

Funding Information:
Funding: This research was supported by a grant (22203MFDS406) from the Ministry of Food and Drug Safety in 2022, the Bio & Medical Technology Development Program (NRF-2022M3E5F1018529) and the Intramural Research Program of KIST.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.


  • cancer therapy
  • cell-penetrating peptide
  • mRNA
  • nucleic acid delivery system

ASJC Scopus subject areas

  • Pharmaceutical Science


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