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The key role of the protein corona: mRNA delivery system undergoes 'identity transformation' in the body, achieving organ targeting | Dr. Janice Zang presentation at BioCon.

Apr 10, 2024

From April 10th to 11th, 2024, the 11th BioCon China Expo International Biopharmaceutical Conference and Exhibition was held in Beijing. Dr. Janice Zang was invited to deliver a keynote speech titled "Nanoparticle Delivery Systems' 'Identity Transformation' In Vivo—Advances in Targeted Nucleic Acid Delivery Technology" at the Innovation and Development of Nucleic Acid Delivery Systems forum. The presentation covered an in-depth exploration of the applications, challenges, and innovations of mRNA technology.

Dr. Zang first outlined the development history and clinical applications and advancements of mRNA technology, including recent clinical data released by Moderna for mRNA-3927, a propionic acidemia enzyme replacement drug, and the latest personalized tumor vaccine results presented by BioNTech and Professor Vinod Balachandran of Sloan Kettering at AACR, which produced a durable immune response in pancreatic cancer patients for up to three years.

Next, Dr. Zang began to elaborate on the basic strategies of achieving organ targeting in vivo with mRNA delivery systems, including active, passive, and endogenous targeting, and introduced the concept of "identity transformation" achieved through a "protein corona," explaining how a synthetic nanoparticle can transform into a biological nanoparticle in the circulatory system of the body.

She pointed out that nanocarriers achieve precise delivery of nucleic acid drug molecules to corresponding organs and tissues by binding with different proteins such as plasma proteins in vivo, utilizing endogenous trafficking mechanisms, thereby improving the biological utilization and therapeutic effects of mRNA. Through LC/MS/MS technology, decoding of the protein corona of some LNP nanoparticles has been achieved, providing explanations for the biological particle characteristics resulting from different component structures. ReCode Therapeutics, a Silicon Valley-based company, reshapes particle properties based on the "fifth component," achieving a change in the composition and physicochemical properties of the traditional LNP system with its SORT LNP system, attracting different "protein coronas" attachment in vivo and better targeting extraliver organs.

Multi-component LNP delivery technology is widely used in COVID vaccines and other mRNA clinical products, but its inherent limitations, such as stability, safety, and targeting, are also evident. In recent years, scientists have increasingly focused on polymersomes to comprehensively optimize mRNA delivery systems. Compared with small molecule cationic lipids (LNP components), polymersomes have better stability and modifiability by connecting each cationic group or lipid group through chemical bonds. The molecular weight of the polymer itself also makes the particle structure of polymersomes more stable.

The ChARLS system developed by the N1 Life team adopts a multi-polymer single-component system. Dr. Zang emphasized the design concept of the ChARLS system, which uses chemical bonds to string multiple functional modules together, improving the functional efficiency of carrier materials while achieving targeting, dissolution, encapsulation, protection, and release. The ChARLS system establishes a correlation between chemical language (molecular structure) and biological language (biological function), with the "protein corona" formed around nanoparticles as the intermediary. Thus, a set of rational design rules for mRNA delivery carriers is established, achieving targeted delivery to multiple organs such as the lungs, spleen, and liver. Currently, this technology has been validated in various animal models and has established technical cooperation with multiple biopharmaceutical companies to apply it to in vivo mRNA therapy, gene editing, and cell therapy fields.

Finally, Dr. Zang reiterated that achieving targeted in vivo delivery is still a peak that scientists worldwide are climbing. The in vivo environment is complex, with vast unknown molecular pathways and biological information. Research on the "protein corona" and targeted delivery technology is still in its early stages and requires joint efforts from the entire industry.

The speech by Dr. Janice Zang  aroused widespread attention and active discussion among participants. Many expressed keen interest in the concept of "identity transformation" of nanoparticle delivery systems in vivo and the application prospects of mRNA delivery technology she proposed. This presentation also provided new ideas and inspirations for researchers in the CGT field. N1 Life looks forward to continuing to advance together with all colleagues, exploring the forefront of delivery technology.

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