Shellac-Mediated Assembly of Nanoparticles for mRNA Delivery

Area of Science:

• Biotechnology
• Materials Science
• Molecular Biology

Background:

• Cationic polymers are widely researched for messenger RNA (mRNA) delivery, but face a tradeoff between high transfection efficiency and significant cytotoxicity.
• High-molecular-weight polymers offer good transfection but cause toxicity, while low-molecular-weight polymers are less toxic but less effective.

Purpose of the Study:

• To develop a versatile and safe mRNA delivery system by addressing the inherent toxicity-efficiency tradeoff of cationic polymers.
• To utilize shellac (SL) as a stabilizing agent for mRNA complexed with low-molecular-weight cationic polymers.

Main Methods:

• A shellac (SL)-mediated assembly strategy was employed to create mRNA-loaded nanoparticles.
• Messenger RNA was complexed with low-molecular-weight cationic polymers and subsequently stabilized by SL under mild conditions.

Main Results:

• The resulting SL-based nanoparticles demonstrated over 90% mRNA encapsulation efficiency.
• These nanoparticles facilitated mRNA transfection across diverse cell types with negligible cytotoxicity.
• The platform successfully enabled protein expression and gene editing in mice following both intravenous and oral administration.

Conclusions:

• Shellac (SL) serves as a crucial component for directing the assembly and delivery of mRNA.
• The SL-based nanoparticle platform offers a modular and versatile solution for nucleic acid delivery.
• This approach holds significant potential for various biological applications requiring efficient and safe mRNA delivery.