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On January 23, the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) released the “Technical Guidance for Nonclinical Studies of Preventive mRNA Vaccines.” This guidance provides detailed explanations on test items, pharmacology, biodistribution, safety, and new LNP (lipid nanoparticles) lipids, offering important references for the nonclinical studies of mRNA vaccines.

In recent years, the mRNA field has achieved several breakthroughs, including the development of different mutants of T7 RNA polymerase, innovative process routes, and clear quality control items and detection methods, all of which have propelled the advancement of the mRNA field.

Hzymes, as the vice president unit of the China Association for the Promotion of Food and Drug Enterprise Quality and Safety, has led the compilation of mRNA quality control detection methods and standards in collaboration with several leading domestic mRNA companies and well-known universities. These efforts have resulted in the development of detection methods and standards for dsRNA quantification, DNase residual detection, RNase residual detection, and T7 RNA polymerase residual detection.

The “Quantitative Detection of dsRNA Impurities in mRNA Vaccines and Drugs by ELISA” includes the design, synthesis, structural modification, and preparation technology of dsRNA standards, value assignment of dsRNA standards, stability evaluation of dsRNA standards, antibody pair screening, ELISA method validation, and ELISA detection.

The “Detection of DNase Residuals in Biological Products by Nucleic Acid Fluorescent Substrate Method” and the “Detection of RNase Residuals in Biological Products by Nucleic Acid Fluorescent Substrate Method” cover the principles of the methods, analytical procedures, and result analysis and judgment.

The “Guidelines for the Development of (Cellular) Immunotherapy Products Based on mRNA-LNP Technology” (T/FDSA 0055-2024) was officially released in November.

The detection methods for dsRNA, DNase, RNase, and T7 RNA polymerase residuals developed by Hzymes are also included in this standard. This standard provides detailed technical routes, preparation processes, inspection methods, quality control points, and functional verification for the development of (cellular) immunotherapy products based on mRNA-LNP technology. It also stipulates the requirements for management, organization, personnel, facilities, equipment, and materials needed for research and production. This standard offers clear technical guidance and product specifications for research institutions and manufacturing enterprises, especially in terms of product design and quality control indicators for different technical routes, with the aim of promoting continuous optimization and innovation of mRNA-LNP technology.

New Product Breakthroughs of Hzymes in 2024

T7 RNA Polymerase (Low dsRNA)

In response to the need for reduced dsRNA residuals in mRNA technology, a GMP-grade raw enzyme with extremely low dsRNA content has been developed. This innovation reduces immunogenicity and enhances drug safety. In 2024, it has already completed pilot-scale production verification in multiple companies and is gradually advancing to the clinical application stage.

T7 RNA Polymerase (Thermostable)

A thermostable T7 RNA polymerase with multiple site mutations has been constructed, which maintains stable activity at temperatures ranging from 37°C to 55°C. Utilizing this thermostable enzyme enables efficient synthesis of circular RNA with a cyclization rate exceeding 90%, while also reducing the production of immunostimulatory by-products such as dsRNA.

dsRNA Detection Kit 2.0

Through continuous in-depth research with mRNA companies and regulatory authorities on mRNA quality control, and after extensive method development and rigorous validation, improvements have been made in the precision, specificity, comprehensive detection of different length fragments, and stability of the detection kit.

T7 RNA Polymerase Residual Detection Kit

An independently developed T7 RNA polymerase residual detection kit has been launched. Using a one-step enzyme-linked immunosorbent assay (ELISA), it can accurately detect the residual amount of T7 RNA polymerase in samples within 1 hour and 15 minutes. It is also compatible with T7 RNA polymerases from other manufacturers.

Fast LNP Ready-to-Use Encapsulation Reagent

Breaking through the limitations of traditional microfluidic encapsulation equipment, the Fast LNP ready-to-use encapsulation reagent allows for the assembly of mRNA-LNP by simply mixing manually. The reagent does not contain ethanol, ensuring high safety. It eliminates the need for complex downstream ultrafiltration and purification processes, as well as complicated sample quality inspection procedures. With Fast LNP, the cost and cycle time for mRNA expression validation can be significantly reduced.

Research and Production Synergy to Drive Field Exploration

High-quality and stable mRNA products serve research in the scientific field, and the continuous optimization and validation of mRNA products during the research process provide reliable assurance for their rapid industrial transformation and application. As research continues to deepen, mRNA products are bound to shine in more fields, driving the development of life sciences to new heights.