Leveraging high-throughput screening technologies in targeted mRNA delivery.

Area of Science:

• Biotechnology and Pharmaceutical Sciences
• Molecular Medicine
• Drug Delivery Systems

Background:

• Messenger ribonucleic acid (mRNA) therapeutics show great promise but face delivery challenges, including liver accumulation and poor targeting.
• Lipid nanoparticles (LNPs) enhance mRNA stability and efficiency, yet targeted delivery to specific tissues remains a significant hurdle.
• Current targeting strategies often lack the scale and efficiency needed for comprehensive optimization.

Purpose of the Study:

• To review conventional low-throughput targeting strategies for mRNA delivery.
• To summarize recent advancements in high-throughput screening (HTS) for mRNA targeted delivery.
• To explore HTS applications in extrahepatic systemic diseases and discuss future challenges and solutions.

Main Methods:

• Overview of traditional low-throughput mRNA targeting methods.
• Detailed summary of HTS techniques for optimizing LNP structures and surface ligands.
• Analysis of HTS applications for systemic mRNA delivery and administration route selection.

Main Results:

• HTS enables large-scale synthesis and validation of chemical compound libraries for mRNA delivery systems.
• Advancements include optimizing delivery vehicle structures and developing extensive surface ligands via HTS.
• HTS facilitates the application of targeted mRNA delivery for extrahepatic systemic diseases.

Conclusions:

• High-throughput screening is a pivotal technology for overcoming mRNA delivery barriers and enhancing therapeutic targeting.
• HTS accelerates the development of sophisticated delivery systems and ligands for diverse therapeutic applications.
• Addressing current challenges in HTS and administration routes will unlock the full potential of mRNA targeted therapy.