This division is composed of 6 teams, 13 professors and more than 100 staff members. Aiming at important national demand, the team prepare high value-added bioformulations and biomaterials by taking natural polysaccharides, proteins, lipids and inorganic substances as raw materials through the process of extraction and separation, controllable degradation and modification, assembly and particulation, which can be used in the fields of preventive / therapeutic vaccines, long-acting / targeted medicines, plant / animal vaccines and immune enhancing foods.

In 2021, the division made new breakthroughs in basic and applied research. 83 papers were published in peer-reviewed leading SCI journals of Nat. Nanotechnol., Nat. Biomed. Eng., Sci. Transl. Med., etc. with 16 papers’IF > 20 and 34 papers’ IF > 10. The division members have undertaken more than 70 projects including Science Fund for Creative Research Groups of the National Natural Science Foundation of China and National Key R&D Projects (including two new projects). In the construction of the team, Prof. Ma Guanghui was elected as an academician of the Chinese Academy of Sciences, Prof. Wei Wei won the support of Beijing Outstanding Youth Fund, and Prof. Xia Yufei won the support of the Youth Talent Promotion Project of Beijing Association for Science and Technology.

Breakthrough 1: A drug sustained release microsphere formulation with uniform size (RF16001 for injection) developed by this division in cooperation with Beijing Huili and Yichang Renfu Pharmaceutical Co., Ltd. has obtained the clinical trial approval. The preparation of microspheres with uniform particle size has always been one of the "neck sticking" technologies in the field of biomedicine in China, and the application of this technology in the field of long-term analgesic drugs is a blank. This product is the first uniform sustained-release microspheres formulation for long-term analgesia in China.

Fig. 1 The GMP pilot workshop, SEM of the microspheres formulation and the registered batch production samples 

Breakthrough 2: Progress in personized therapy of tumor. (1) A novel strategy using lymph node-tumor dual targeting exosomes for synergistic tumor immunotherapy was proposed. In multiple animal tumor models (lymphoma, breast cancer and melanoma), chimeric exosome showed efficient inhibition of primary tumors, tumor metastases, and postoperative tumor recurrence, outperforming both a current adoptive T cell transfer therapy and a cancer vaccination treatment (Sci. Transl. Med., 2021, 13, eabb6981). Corresponding clinical trial has been initiated in Fudan University Pudong Hospital. (2) Based on polylactic acid (PLA) self-healing microcapsule, a novel high-performance cancer vaccine was constructed by utilizing the special “post-encapsulation” approach to provide a mild and efficient paradigm for antigen microencapsulation. After a single subcutaneous injection, effective T cell responses and potent tumor inhibition for multiple solid tumors and leukemia are achieved with excellent safety (Nature Biomedical Engineering, 2021, 5: 414).

Fig. 2 Preparation of macrophage-tumor chimeric exosomes and tumor inhibition mechanism

Breakthrough 3: New plant resistance-inducer biopesticides (plant vaccine) with novel oligosaccharide structures were successfully developed. The "green and clean” production strategy was fully applied to the precisely controlled preparation process of the oligosaccharide products. Based on the joint multi-omics analysis, we have clarified the plant immunity induction mechanism of highly active chitosan, which affected plant metabolic changes to enhance resistance. The key metabolite 4-ABA for the oligosaccharide-induced insect resistance of plants was identified. Based on these works, four new biopesticide registrations were approved by the Ministry of Agriculture and Rural Affairs of China, including two new active compound registrations. Among them, a hetero-chitooligosaccharide DACOS, which has a strong plant immune-inducing anti-insect activity, can effectively help plants resist insect pests by targeting the plant's potential. To date, no such type of biopesticide has been found in the US EPA and EU EFSA pesticide registration database. DACOS is the world-first registered plant immunity inducer biopesticide with insect-repellent activity.

Fig. 3 Standardized field trials and pesticide registration certificates (China) for the two new oligosaccharide biopesticides (NACOS and DACOS)