生物治療全國(guó)重點(diǎn)實(shí)驗(yàn)室

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(jiǎn)介

?????生物治療是現(xiàn)代生物技術(shù)與臨床醫(yī)學(xué)等多學(xué)科交叉融合而形成的針對(duì)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(jìn)行治療研究的新興領(lǐng)域。生物治療研究范圍非常廣泛，主要包括針對(duì)重大疾病的生物技術(shù)藥物、基因治療、免疫治療(疫苗治療、抗體治療、細(xì)胞因子治療等)、調(diào)節(jié)血管生成治療、干細(xì)胞及組織工程治療、誘導(dǎo)分化及凋亡治療等相關(guān)的基礎(chǔ)研究、應(yīng)用基礎(chǔ)研究、關(guān)鍵技術(shù)及產(chǎn)品研發(fā)等。

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????生物治療國(guó)家重點(diǎn)實(shí)驗(yàn)室的總體定位是將現(xiàn)代生物技術(shù)、臨床醫(yī)學(xué)、免疫學(xué)、藥物學(xué)、納米生物技術(shù)、化學(xué)、材料學(xué)等多學(xué)科進(jìn)行交叉與融合，致力于人類重大疾病生物治療的基礎(chǔ)研究、應(yīng)用基礎(chǔ)研究、關(guān)鍵技術(shù)及產(chǎn)品研發(fā)，建設(shè)國(guó)內(nèi)一流、國(guó)際知名的生物治療實(shí)驗(yàn)室，促進(jìn)醫(yī)藥生物技術(shù)的發(fā)展。目前，已建立了從基因發(fā)現(xiàn)到藥物研發(fā)及臨床治療等一系列關(guān)鍵技術(shù)平臺(tái)，如基因組學(xué)、蛋白質(zhì)組學(xué)、模式生物（基因工程小鼠、斑馬魚(yú)與非洲爪蟾）；生物技術(shù)藥物、基因治療、干細(xì)胞與組織工程、納米生物技術(shù)、化學(xué)生物學(xué)、天然小分子藥物、計(jì)算機(jī)輔助藥物設(shè)計(jì)等藥物研發(fā)關(guān)鍵技術(shù)平臺(tái)；已建成了生物技術(shù)藥物及天然藥物的GMP中試生產(chǎn)車間、國(guó)家新藥臨床前評(píng)價(jià)中心和國(guó)家新藥臨床試驗(yàn)基地（生物治療）。形成了以下5個(gè)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(diǎn)研究針對(duì)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(tǒng)疾病、遺傳病等的生物治療。

????2．功能基因組學(xué)及蛋白質(zhì)組學(xué)研究：重點(diǎn)發(fā)展和完善基因組學(xué)、蛋白組?學(xué)和生物信息學(xué)的研究平臺(tái)，結(jié)構(gòu)生物學(xué)、表觀遺傳學(xué)、建立模式生物、基因敲除平臺(tái)，重點(diǎn)進(jìn)?行重要致病基因的克隆、鑒定及突變分析與基因多態(tài)性的研究；免疫應(yīng)答分子機(jī)理研究；信號(hào)傳導(dǎo)與細(xì)胞凋亡研究等，為人類重大疾病生物治療奠定理論基礎(chǔ)及提供新的靶分子。

???3．干細(xì)胞與組織工程研究：重點(diǎn)研究人胚胎干細(xì)胞、骨髓基質(zhì)干細(xì)胞、造血干細(xì)胞、肌肉干細(xì)胞和脂肪干細(xì)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(fù)（主要采用工程化組織替代及誘導(dǎo)組織再生技術(shù)，重點(diǎn)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(jié)律的重建，冠心病的補(bǔ)片材料）。

???4．化學(xué)生物學(xué)/化學(xué)基因組學(xué)及納米生物技術(shù)研究：重點(diǎn)研究特異性小分子的設(shè)計(jì)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(kāi)發(fā)等；研究靶向式藥物釋放（微納米）載體（膜）技術(shù)、可控降解藥物膠囊材料與系統(tǒng)、研究靶向藥物與新型給藥系統(tǒng)。

???5．新藥臨床前評(píng)價(jià)和新藥臨床試驗(yàn)（生物治療）：主要開(kāi)展的生物治療?臨床研究有造血干細(xì)胞移植、細(xì)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(guó)家新藥臨床試驗(yàn)基地，已承擔(dān)了多項(xiàng)抗腫瘤生物技術(shù)新藥的臨床試驗(yàn)研究。