Westlake University and Zhejiang University co-hosted the 2023 Forum on Nucleic Acids and Delivery Systems on Feb. 11 and 12.

Over 40 leading researchers and industry leaders gathered in Hangzhou and discussed the trends and challenges in the nucleic acid delivery system. The conference covered new materials for nucleic acid delivery, nucleic acid modification technology, nucleic acid targeted therapy, and the transformation and application of nucleic acid drugs.

Keynote Speeches

Prof. Xuesi Chen from the Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, and Prof. Weihong Tan from the Institute of Basic Medicine and Oncology, Chinese Academy of Sciences, were invited to the conference to share their research and experience.

Chen shared his latest progress in cancer immunotherapy and nucleic acid delivery materials. Chen’s team discovered that by modifying heterocyclic molecules (PEI-M) through polyethyleneimine (PEI), they could efficiently enhance the stability of antigen loading and the immunostimulatory activity of the incubation material itself. Such immunostimulatory polyethyleneimine-like material could be used as the adjuvant materials for new vaccines or nucleic acid delivery. Golden Tran, the gene transfection reagents developed by Chen’s team, achieved significantly better performance over those from international peers in biocompatibility, stability, operability, and cost. Their findings would greatly reduce the cost of conducting relevant research in China and decrease the reliance on imported reagents.

Tan shared his groundbreaking concept of designing molecular elements based on nucleic acids, also known as the modular synthesis of programmable functionally active molecules. Inspired by the periodic table of elements, Tan established a periodic table of molecular elements (nucleic acid bases) and analyzed the design and synthesis of functional molecules and their potential applications. His team had persevered through the restrictions on antibody and drug covalent linking strategy and provided new direction to the targeted therapy for tumors.

New Molecular Delivery Material

Prof. Jun Wang from South China University of Technology spoke about his research on nucleic acid drug delivery solutions, the main challenge in applications. Wang developed a series of functional polymer carriers showing great potential in this field.

Prof. Yezi You from University of Science and Technology of China shared his findings on the synthesis and delivery of cell-membrane perforating nucleic acid vectors. His team developed a carrier that could puncture the cell membrane and open direct passage into the cells, in turn effectively enhancing the transfection efficiency.

Prof. Chuan Zhang from Sichuan Jiaotong University brought his latest work on the design and delivery of a new type of nucleic acid-based drug. Building on the DNA structure, Zhang’s team created various nanogels through supramolecular assembly, which could be used for tumor treatment, as well as for eye diseases in the form of macroscopic injectable gels.

Prof. Lichen Yin from Suzhou University shared his findings on macromolecular drug transmembrane delivery system. Through regulating the polypeptide secondary structure, Yin’s team gave the polymer material a selective membrane penetration, and were able to load the nucleic acid drugs with an intricate structural design.

Prof. Xintao Shuai from Sun Yat-sen University showcased a collection of highly efficient nucleic acid delivery vectors. He believed that working with clinical physicians would help researchers discover the pressing issues. He also encouraged students to combine their knowledge with the experience of clinical physicians on sustainable work.

New Technologies for Nucleic Acid Delivery

The conference moved on to new technologies for nucleic acid delivery in the afternoon of Feb. 11. Prof. Xiqun Jiang from Nanjing University gave a speech on the high-efficiency, dual-targeting protein-drug conjugate for treating tumors. Through the innovative design of genetic reprogramming, they combined functional protein or polypeptide and elastin-like protein and studied the characters of the structure and physical and chemical properties of the synthesized biomacromolecules.

Prof. Guangjun Nie from National Nanoscience Center shared recent work on the precise regulation of multiple factors affecting tumor immunotherapy, the development of broadly adaptable tumor vaccines, and the maximization of the immune system.

Prof. Shaobin Zhou shared his progress on multifunctional polymer carriers for anti-tumor drug delivery. To increase the efficacy, Zhou’s team prepared a collagenase-modified polymer micelle with variable size and a pH responsive polymeric vesicle to combat the tumor and the metastasis. The outward targeting membrane vesicles they developed could trigger the automatic blocking at the immune checkpoint and enhance the treatment response.

Prof. Yue Zhang of Westlake University shared three membrane protein-mediated delivery systems developed from the cell membrane biomimetic nanotechnology. Zhang’s team achieved specific adhesion to tissues using membrane proteins of prokaryotic and eukaryotic cells. They also designed a double-membrane hybrid system to optimize the types and functions of membrane proteins on nanoparticles. In addition, they developed a drug encapsulation technology in cell membrane vesicles to achieve smart and efficient drug delivery.

Prof. Zhuang Liu from Suzhou University shared progress in immune engineering based on DNA engineering technology. Liu’s team developed a novel anti-tumor pharmaceutical preparation that induced endogenous tumor vaccines in vivo, and various novel nanoprobes. With the explorations of new treatment strategies based on nanotechnology and biomaterials, Liu hoped to make tumor immunotherapy more accurate and effective.

Prof. Xin Zhang from Westlake University shared findings on the chemistry of bioaggregates. Zhang's team developed a series of new quantitative imaging technologies for protein aggregation and protein homeostasis in living cells, resolved key issues related to protein aggregation, and revealed the functions of small molecule drugs on protein aggregation and protein homeostasis, shedding light on the diagnosis and treatment of major diseases.

Prof. Shuai Liu’s team of Zhejiang University developed ionizable phospholipid structures that promoted membrane instability, which enhanced endosome escape and mRNA delivery efficiency. They then built an LNPs pool and achieved lung-, spleen- and liver-specific mRNA delivery and gene editing by regulating the structure of phospholipids or changing the composition of auxiliary lipids in LNPs. When exploring the carrier system aside from LNPs, they developed a lipidized zwitterionic polymer pool, which helped them to selectively deliver to lymph nodes and the spleen and had great potential in immunology application.

Nucleic Acid Targeted Therapy

Seven more presentations were made on the topic of nucleic acid targeted therapy in the morning of Feb. 12.

Facing the existing challenge of poor protein stability, Prof. Yiyun Cheng’s team from East China Normal University developed novel polymer carriers enhanced by non-covalent interaction. Taking advantage of the excellent self-assembly performance and transmembrane ability of fluorine-containing polymers to deliver proteins, Cheng’s team applied the findings to various disease models.

Prof. Yongming Chen’s team from Sun Yat-sen University shared significant progress in the application of delivery material and techniques in nanomedicine and vaccine/adjuvant and gene delivery carriers. Proposing that the cell-free nucleic acid was an important factor causing autoimmune response, they also came up with the idea to suppress immune responses by scavenging free nucleic acids using cationic polymers, which saw positive results in animal testing.

Prof. Yuan Ping from Zhejiang University focused his research on the carrier for efficient delivery of gene editing tools, including nucleic acids, mRNA, and ribonucleoproteins. His team developed a drug carrier material that stabilized protein drug activity and ensured effective delivery to the lesion site.

Prof. Yaoxin Lin from the National Center for Nanoscience and Technology shared his research progress and application of mRNA smart nano-delivery machines. By building a pool of polypeptide-based nano-delivery systems and lipid nanoparticle nano-delivery systems, his team developed and maximized the polypeptide-polymer nano-delivery system and liposome hybrid nano-delivery system.

Prof. Zhen Gu shared the progress his team made in the design of precise drug delivery systems triggered by physiological signals, explaining how microneedle patches could be used to regulate blood sugar in a physiological environment and the development of remote precise delivery of treatments by drones. Gu also spoke about the immunotherapy research he conducted using platelets.

Prof. Huayu Tian from Xiamen University shared his findings on a polymer nucleic acid delivery system based on multiple interactions, noting that polymers have a unique advantage in loading and delivering nucleic acids. His team developed a series of polymer polypeptide carrier materials, including gene transfection reagents for cells, which were commercialized.

Prof. Huaimin Wang from Westlake University spoke on the programmable assembly and functional regulation of peptides. Wang’s team made progress on the in-situ construction of functional peptide assemblies. He emphasized how they utilized endocytosis pathways to construct polypeptide self-assembly systems that specifically target lysosomes, and how they managed to selectively inhibit cancer cells in the preliminary stage, improving the efficacy of existing target drugs.

Commercialization and Application of Nucleic Acid Drugs

Prof. Xingjie Liang, Prof. Dongsheng Liu and Prof. Yucai Wang shared their thoughts on bottlenecks and solutions for nucleic acid delivery technology research and transformation, the development and application of modular nano-drug delivery system technology, and ideas for drug delivery carriers from basic research to enterprise transformation in the afternoon of Feb. 12.

Two representatives from the industry, Prof. Zicai Liang from Ribolia and Prof. Haifa Shen from Stemirna, talked about the current research and development progress of nucleic acid carrier technology and patent strategy at home and abroad. LNP and similar drugs and genetic delivery carrier technology have been patented in the U.S. They emphasized efficacy and safety as the priorities in nucleic acid drug development. They also expressed concerns about the national biosafety technology reserve and high expectations for the development of patented original polymer drugs .

Roundtable:

“What roles will researchers play in the field of nucleic acid delivery material in the future?”

A vibrant discussion about basic research on nucleic acid delivery materials and technologies took place among participants, including Prof. Xuesi Chen, Prof. Jun Wang, Prof. Shuai Liu, Prof. Chuan Zhang, Prof. Fujian Xu and Prof. Linqi Shi. They reviewed the development of medical materials such as LNP and polymers in the field of nucleic acid delivery and shared their opinions on the future of this field.

The second roundtable, about nucleic acid drug transformation and application,  was moderated by Dr. Peizhuo Zhang, chief scientist of Gene Pharma. The participants believed that, in the future, the field should focus on developing new carriers for gene nucleic acid delivery and breaking through international technical barriers, consistent with government recommendations.

Over two days, the  2023 Forum on Nucleic Acids and Delivery Systems ignited curiosity and passion for research. As Prof. Xuesi Chen said in his speech, the era of nucleic acid drugs has arrived. This marks the third wave of drug research and development in the century, with more to come in the future. Delivery systems are the key technology for nucleic acid therapy, which will develop from vaccines to therapeutic drugs. With the changes in dosage and administration methods, great room for the development of nucleic acid delivery technology still remains.