Intracellular delivery strategies using membrane-interacting peptides and proteins

Area of Science:

• Biotechnology
• Molecular Biology
• Drug Delivery

Background:

• Cellular cytosol and organelles are key targets for disease treatments.
• Delivering large biomacromolecules like proteins and nucleic acids to these sites is challenging due to membrane permeability.
• Existing delivery systems face limitations in efficiently crossing cellular barriers.

Purpose of the Study:

• To review recent advances in peptide and protein-based strategies for cytosolic delivery of biomacromolecules.
• To discuss current challenges and opportunities in leveraging cell membrane interactions for therapeutic delivery.
• To explore both naturally derived and de novo designed peptide/protein delivery systems.

Main Methods:

• Review of current literature on peptide and protein delivery systems.
• Analysis of strategies involving cell membrane association and modulation.
• Categorization of approaches including natural, inspired, and de novo designs.

Main Results:

• Peptide and protein systems show significant potential for overcoming cell membrane barriers.
• These systems offer advantages in interacting with and modulating cell membranes for cargo entry.
• Diverse strategies exist, ranging from natural sequences to engineered de novo designs.

Conclusions:

• Peptide and protein strategies are effective for enabling cytosolic delivery of therapeutic biomacromolecules.
• Further research into cell membrane interactions is crucial for optimizing these delivery systems.
• Both natural and de novo designed systems hold promise for future therapeutic applications.