Brief Introduction of State/National Key Laboratory of Biotherapy and National Research and Development Platform for Novel Drug

??????State/National Key Laboratory of Biotherapy (SKLB) was established by the Ministry of Sciences and Technology in China in 2005, and became one of the National Research and Development (R&D) Platforms for Novel Drugs founded by the Ministries of Sciences and Technology as well as Public Health in September 2008. It is also supported by National Collaborative Innovation Program and became the National Collaborative Innovation Center for Biotherapy in April 2013. The Platform is located in the High Tech Zone of Chengdu and the Medical Campus of Sichuan University. The overall space is nearly 70,000 square meters and is still under intensive growth and construction. SKLB also has rich clinical resources of West China Hospital, which has 4,300 beds.

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???? SKLB is becoming a highly-regarded, comprehensive?and multidisciplinary research center in China. Through the seamless integration of basic research, preclinical development, translational and clinical medicine, an efficient and fully integrated technology chain for the discovery and development of innovative drug candidates has been established in a single institute. Part of the mission of this Platform is to improve the treatment of major human diseases such as cancer, cardiovascular diseases, obesity, diabetes mellitus, infectious diseases (hepatitis, AIDS, and tuberculosis etc), inflammatory diseases, neurological disease, as well as chronic autoimmune diseases. Focusing on more than 200 important targets, hundreds of projects for basic research and ?biologic drugs (such as gene and cell therapy, vaccines, and monoclonal antibodies, recombinant proteins, etc), synthetic small molecule drugs and small molecule natural products are ongoing.

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????? The Platform boasts a prominent faculty of nearly 100 well-funded full professors, associate professors and assistant professors, with diverse disciplines such as biotechnology, medicine, immunology, pharmacology, chemistry, formulations, drug delivery, and material sciences. Every year the faculty can obtains competitive grants from the government, including the National High Technology Research and Development Program (“863” Program) or the Major State Basic Research Development Program (“973” program). Over 300 research papers are published in peer-viewed international journals every year, including such top journals as New Engl J Med, Nat Rev Drug Discovery, Dev Cell, Nat Chemical Biol, Nature Med, Mol Cell, Proc Natl Acad Sci USA, Cancer Res, and Lancet Neurol. To date, the Platform has licensed over 50 patents to the commercial sector throughout China. Furthermore, 45 potent candidate drugs thus far have been transferred to over 30 pharmaceutical companies for commercial development.

????The Platform also provides both key technological services and integral solutions in R&D for other institutions and companies, including:

(1) Target Identification and Drug DiscoveryThe Platform has established multiple sub-platforms, such as?Proteomics and genomics, structural biology, epigenetics, immunology, molecular cell biology，developmental biology，the mechanism of diseases, biopharmaceuticals R&D, gene and cell therapy, monoclonal antibody and vaccine, stem cell/tissue engineering,?engineering mice and zebrafish, drug delivery and nanotechnology,?computer-aided drug design, chemical biology,?screening and synthesis of small molecular drugs, and the separation and purification of active natural products,?especial in the development of novel therapeutic approaches. ?????? ???????? ???????? ????????? ???????? ????(2) Pilot-Scale Production Six GMP-level facilities for pilot-scale production of adenoviral vectors, vaccines, DNA plasmids, recombinant proteins and nanoparticles have been established. For example, the pilot-scale production of DNA plasmids provides 5000-8000 doses for early phase clinical trials. ??????? ???(3) Pharmacodynamics & Pharmacokinetics Three separate animal facilities can maintain up to 60,000 mice. At full capacity, 300 drug candidates can be evaluated at the same time. To date, there have been over 100 different preclinical disease models established at these facilities.

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??(4) Pre-Clinical Safety Evaluation The animal center has currently obtained international“AAALAC”accreditation. The GLP facility can maintain up to 500 monkeys. Various toxicity studies including single dose toxicity, repeated dose toxicity, reproductive and developmental toxicity, genotoxicity, carcinogenicity, immunogencity, and pharmacokinetic/toxicokinetic (PK/TK) analyses are all performed. ?? ???(5) Clinical trials Clinical trials testing gene and cell therapy, cytokines and anti-cytokines, monoclonal antibodies, chemotherapy and targeted small molecule drugs are conducted in the clinical units of West China Hospital with 4300 beds. ? ???(6) Graduate programs The platform also is an educational center. Every year the platform enrolls about 150 Ph.D and 100 M.S students for different academic programs, as well as nearly 100 M.S. graduate students for pharmaceutical engineering programs. ?

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?????????????????????????????????????????????????????????????????????????????????研究方向簡介

?????生物治療是現代生物技術與臨床醫學等多學科交叉融合而形成的針對人類重大疾病，如腫瘤、心腦血管疾病、感染性疾病、自身免疫性疾病等進行治療研究的新興領域。生物治療研究范圍非常廣泛，主要包括針對重大疾病的生物技術藥物、基因治療、免疫治療(疫苗治療、抗體治療、細胞因子治療等)、調節血管生成治療、干細胞及組織工程治療、誘導分化及凋亡治療等相關的基礎研究、應用基礎研究、關鍵技術及產品研發等。

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????生物治療國家重點實驗室的總體定位是將現代生物技術、臨床醫學、免疫學、藥物學、納米生物技術、化學、材料學等多學科進行交叉與融合，致力于人類重大疾病生物治療的基礎研究、應用基礎研究、關鍵技術及產品研發，建設國內一流、國際知名的生物治療實驗室，促進醫藥生物技術的發展。目前，已建立了從基因發現到藥物研發及臨床治療等一系列關鍵技術平臺，如基因組學、蛋白質組學、模式生物（基因工程小鼠、斑馬魚與非洲爪蟾）；生物技術藥物、基因治療、干細胞與組織工程、納米生物技術、化學生物學、天然小分子藥物、計算機輔助藥物設計等藥物研發關鍵技術平臺；已建成了生物技術藥物及天然藥物的GMP中試生產車間、國家新藥臨床前評價中心和國家新藥臨床試驗基地（生物治療）。形成了以下5個主要研究方向：

????1. 腫瘤、感染性疾病等重大疾病生物治療研究：重點研究針對腫瘤、感染性疾病（如肝炎、HIV、等）、心血管疾病、自身免疫疾病、呼吸系統疾病、遺傳病等的生物治療。

????2．功能基因組學及蛋白質組學研究：重點發展和完善基因組學、蛋白組?學和生物信息學的研究平臺，結構生物學、表觀遺傳學、建立模式生物、基因敲除平臺，重點進?行重要致病基因的克隆、鑒定及突變分析與基因多態性的研究；免疫應答分子機理研究；信號傳導與細胞凋亡研究等，為人類重大疾病生物治療奠定理論基礎及提供新的靶分子。

???3．干細胞與組織工程研究：重點研究人胚胎干細胞、骨髓基質干細胞、造血干細胞、肌肉干細胞和脂肪干細胞等；研究工程化組織替代（包括骨、軟骨、肌腱、皮膚、角膜）、消化及泌尿管道的再生與修復（主要采用工程化組織替代及誘導組織再生技術，重點是食管、膀胱、尿道、膽道）；心臟病的治療（包括心肌缺血的再生，組織工程人工心瓣，異位節律的重建，冠心病的補片材料）。

???4．化學生物學/化學基因組學及納米生物技術研究：重點研究特異性小分子的設計與合成、小分子與大分子間的相互作用及生物活性、小分子靶向抗腫瘤藥物的開發等；研究靶向式藥物釋放（微納米）載體（膜）技術、可控降解藥物膠囊材料與系統、研究靶向藥物與新型給藥系統。

???5．新藥臨床前評價和新藥臨床試驗（生物治療）：主要開展的生物治療?臨床研究有造血干細胞移植、細胞因子治療、抗體治療以及多種生物化療方案等。該研究中心作為國家新藥臨床試驗基地，已承擔了多項抗腫瘤生物技術新藥的臨床試驗研究。