Overview
RinuaGene Biotechnology Co., Ltd. (hereinafter referred to as "RinuaGene") has published a research paper on its independently developed novel ionizable cationic lipid, (4S)-KEL12, in the internationally renowned journal Advanced Science. The paper, titled "Discovery of Ketal-Ester Ionizable Lipid Nanoparticle with Reduced Hepatotoxicity, Enhanced Spleen Tropism for mRNA Vaccine Delivery," is available at https://onlinelibrary.wiley.com/doi/10.1002/advs.202404684. RinuaGene and the Institute of Medicinal Biotechnology at the Chinese Academy of Medical Sciences & Peking Union Medical College are joint corresponding authors of the article.
The success of mRNA vaccines has demonstrated the immense potential of mRNA technology in the biomedical field. LNP delivery technology based on ionizable cationic lipids is the current mainstream mRNA delivery method that has been clinically applied and is a core technology in mRNA vaccine development. Due to the lack of clarity regarding the LNP delivery mechanism and the structure-activity relationship of lipids, as well as high patent barriers, the development of safe and effective mRNA vaccine delivery lipids has always been one of the hot research topics and challenges in the field.
This study employed a development strategy of introducing biodegradable groups and iteratively optimizing key structural components to design and synthesize a series of novel ketal-ester lipids (KELs) to improve their safety and delivery performance. Compared to the mainstream international SM-102 LNP, the representative lipid (4S)-KEL12 LNP exhibits a better safety profile, including low expression in the liver, reduced hepatotoxicity, and good biodegradability. At the same time, this novel n LNP also shows outstanding targeting of immune organs and cells. When delivering mRNA therapeutic cancer vaccines, it can effectively inhibit tumor growth and perform excellently on key immunological indicators. The research shows that the novel ketal-ester lipid LNP represented by (4S)-KEL12 is a safe and efficient delivery system with broad application prospects in mRNA-related immunotherapies and vaccines. Furthermore, in the development of multiple mRNA products, it has demonstrated distinguished therapeutic effects, indicating the huge potential of this lipid series of LNPs for future clinical applications.
In addition to the ketal-ester lipid series presented in this study, RinuaGene has designed a compound library of ionizable lipids covering over 40 different structural types and tens of thousands of compounds. Through the evaluation of the delivery expression, biodistribution, and toxicology of these candidate compounds, the company has obtained a variety of new lipid candidate molecules that are highly efficient, lower toxic, and tissue-targeted.
RinuaGene will continue to advance the research and development of delivery systems to solve the challenges of mRNA delivery and develop safer and more effective mRNA vaccines. This will promote the continuous clinical application and development of mRNA therapies, while also push mRNA therapies toward a future that is more precise, efficient, and individualized.
About RinuaGene
RinuaGene is dedicated to developing innovative mRNA-based drugs and vaccines to address significant unmet global clinical needs. Our therapeutic vaccine for HPV16 and 18-related tumors received FDA clinical approval in October 2023, with a China IND application already accepted by the CDE. We have also submitted an IND application for a multivalent prophylactic vaccine, and several other infectious disease vaccine candidates are in the IND stage.
We have full-chain, in-house R&D and clinical production capabilities for mRNA drugs and vaccines. Our four core technology platforms are: linear mRNA, circular RNA, targeted LNP delivery, and CMC. RinuaGene has filed more than 70 patents covering our product pipeline, delivery systems, and component design. We are continuously building a comprehensive intellectual property portfolio to establish a strong global patent presence. Through our deep foundational research, we aim to be a leader in mRNA delivery technology.
Upholding our corporate culture of innovation, openness, collaboration, and mutual benefit, we welcome partnerships in various areas, including product development, combination therapies, technology platforms, and novel delivery systems. Together, we can advance the development and application of RNA technology across multiple fields. (bd@rinuagene.com)