Cell-Penetrating Peptides: Emerging Tools for mRNA Delivery

Area of Science:

• Biotechnology
• Molecular Biology
• Vaccinology

Background:

• Messenger RNAs (mRNAs) show significant potential for vaccines and therapies against diseases.
• Effective delivery systems are crucial for enhancing mRNA bioavailability and therapeutic efficacy.
• Cell-penetrating peptides (CPPs) are emerging as advanced carriers for nucleic acid delivery.

Purpose of the Study:

• To review the distinctive features and applications of cell-penetrating peptide (CPP)-based messenger RNA (mRNA) delivery systems.
• To highlight the advantages of CPPs in improving mRNA bioavailability and therapeutic outcomes.
• To discuss the integration of functionalities into CPPs for targeted mRNA delivery.

Main Methods:

• Review of existing literature on CPPs and mRNA delivery systems.
• Analysis of CPP characteristics, including amino acid composition and sequence.
• Examination of reported outcomes of CPP-mediated mRNA delivery in various biological contexts.

Main Results:

• CPPs facilitate enhanced endosomal escape and selective targeting of immune cells like dendritic cells (DCs).
• CPP-based systems enable modulation of endosomal pathways for efficient antigen presentation by DCs.
• Effective mRNA delivery to the lungs via dry powder inhalation and prolonged protein expression through mRNA stabilization have been reported.

Conclusions:

• Cell-penetrating peptides (CPPs) represent a powerful and versatile platform for mRNA delivery.
• CPPs enhance the therapeutic potential of mRNAs by improving delivery, targeting, and stability.
• Further development of CPP-based systems holds promise for innovative vaccines and treatments.