时间：9月8日星期三16:00-17:30    

Time：4:00-5:30 PM，Wed., September 8th，2021

地点：西湖大学云栖校区3号楼312会议室

Venue: Room 312, 3F, Building 3, Yunqi Campus

主持人：西湖大学生命科学学院讲席教授 许田

Host：Dr. Tian Xu, Chair Professor, School of Life Sciences

主讲嘉宾/Speaker:

Prof. Wenxin Wang

The Charles Institute of Dermatology, School of Medicine, University College Dublin, Ireland

Department of Polymer Science and Engineering, Zhejiang University, China

Wenxin Wang is Full Professor in Skin Research and Wound Healing, a Science Foundation Ireland (SFI) Principal Investigator at the Charles Institute of Dermatology, School of Medicine, University College Dublin (UCD), and a member of UCD Academic Council. He won the highly prestigious “Young Scientist Prize in Regenerative Medicine” in 2010 at TERMIS-EU conference, the “SFI Principal Investigator award” in 2011 and the DEBRA Award for Excellent EB Patient Service in 2014, which highlight his work ethic and achievements. Prof. Wang’s scientific interests are in the areas of biomaterials, stem cell and gene therapy for the treatments of skin wounds, cardiovascular and neural degenerative diseases. His scientific contribution and achievements have been recognized both nationally and internationally including over 200 peer-reviewed scientific journal papers (Nat. Commun., Nat. Rev. Chem., Sci. Adv., Angew. Chem., JACS, Chem. Sci. and Nano Letters etc.), 5 book chapters, 22 patents granted, 136 conference abstracts and presentations, and 107 invited lectures and keynote presentations.

讲座摘要/Abstract:

Gene therapy is one of the most promising therapeutics in modern medicine, which has the potential to treat diseases from the "root". Currently, one of the major bottlenecks that hinder the translation of gene therapy from bench to clinical settings is the lack of safe and effective gene delivery vectors. Viral vectors, like adeno-associated virus and lentivirus, usually show high gene transfection efficiency, but their immunogenicity and toxicity have raised major concerns about their application. Non-viral vectors are safer; however, their transfection efficiency is much lower. Therefore, tremendous efforts have been dedicated to developing both efficient and safe non-viral gene delivery vectors.

Advancements in polymer chemistry have led to the design and development of various vectors with different polymeric structures. Most notably, linear poly(β-amino ester)s (LPAEs) have emerged as one of the most versatile types of gene delivery vectors. Since they were first developed in 2000 by Lynn and Langer from Massachusetts Institute of Technology (MIT), more than 2500 LPAEs have been designed, synthesized, and screened. To date, all studies with poly(β-amino ester)s have been focused on their linear structure. Although the results from LPAEs are very encouraging, the potential for synthesizing and optimizing structures with multiple functional groups is limited by the linear nature of these polymers. Branched polymers have a three-dimensional (3D) architecture with multiple functional terminal groups, making them increasingly appealing for biomaterial applications. In the past few years, our group has successfully developed highly branched poly(β-amino ester)s (HPAEs) via a facile one-pot “A2 + B3 + C2” Michael addition strategy. Over a wide range of cell types, HPAEs exhibited much higher gene transfection ability in comparison with corresponding linear counterparts, establishing their greater potential in gene delivery. The outstanding gene delivery ability of HPAEs was further demonstrated in vivo using recessive dystrophic epidermolysis bullosa (RDEB) skin disease models. In both the RDEB knockout mouse model and human RDEB skin graft mouse model, HPAEs mediated high level and up to 10-week restoration of collagen VII (~900KDa) expression and achieved an excellent safety profile, highlighting their huge potential for clinical skin gene therapy. In addition, in vitro and in vivo assays also showed that HPAEs have remarkable ability for CRISPR Cas9 ribonucleoprotein delivery in gene editing strategy. The high efficiency and excellent safety of HPAEs provides valuable insight into their applications in various genetic diseases and demonstrates great prospects for their translation to a clinical environment.

联系人/Contact：

生命科学学院

于文越 yuwenyue@westlake.edu.cn