Chemically or physically introducing lipids into lysine-histidine-based peptide systems for safe, efficient and...

Area of Science:

• Biotechnology
• Materials Science
• Molecular Biology

Background:

• Messenger RNA (mRNA) therapy presents a powerful approach for personalized medicine.
• Developing efficient and cost-effective delivery systems remains a challenge for mRNA therapeutics.

Purpose of the Study:

• To create a versatile and economical mRNA delivery vector by integrating simple peptide and lipid modules.
• To investigate the combined effects of peptide and lipid components on mRNA delivery efficiency both in vitro and in vivo.

Main Methods:

• Synthesized a library of mRNA carriers using chemical lipidation (lipopeptide) and physical lipid incorporation into modular peptides.
• Evaluated mRNA encapsulation, transfection efficiency, and biocompatibility in vitro.
• Assessed mRNA delivery efficiency and tissue selectivity in vivo, particularly for lung delivery.

Main Results:

• Lipid components significantly enhanced mRNA encapsulation and transfection efficiency compared to peptides alone.
• Chemical optimization led to a 5.3-fold increase in transfection efficiency.
• The optimal physical composite system outperformed pure lipid and peptide systems, and surpassed commercial reagents in mRNA expression, showing improved lung selectivity in vivo.

Conclusions:

• The complementary design strategy effectively created simple, highly functional mRNA delivery vectors.
• This approach offers a cost-effective, safe, and efficient platform for advancing mRNA therapeutics, especially for lung-related diseases.