Gene Therapy Innovation and Manufacturing Centre (GTIMC)

基因治疗创新与制造中心（GTIMC）

• 批准号: MR/V030140/1
• 负责人: Mimoun Azzouz
• 金额: $ 871.58万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV030140%2F1
• 关键词: Gene; Therapy; Innovation; Manufacturing; Centre

Gene therapies rely on engineered virus carriers as vehicles for the delivery of synthetic genes that allow correction of disease-altered changes in multiple organs of the human body. Viruses exploited in gene therapy approaches have been modified to remove harmful properties and carry the therapeutic gene of interest. Multiple gene therapy programmes are currently undertaken in research laboratories using relatively small-scale production of viruses which enables optimisation of the doses and administration routes as well as testing for the safety and therapeutic efficacy of interventions in animal models of disease. However, facilities required for the production of large quantities of clinical-grade viruses of consistent quality-controlled GMP grade are rare in the UK. Thus, it can easily take several years before clinical trials can be conducted. Currently, existing facilities cannot meet the escalating demand of academically-led research needs for clinical-grade virus carriers. This is significantly obstructing numerous UK-funded world-leading disease-modifying discoveries to be translated into clinical trials for human benefit. The lack of suitable GMP facilities seriously hinders the development of much-needed novel effective treatments for multiple incurable diseases which cannot be treated by conventional drug compounds. We propose to address the manufacturing shortage by creating a Gene Therapy Innovation and Manufacturing Centre (GTIMC) which includes provision of a new state-of-the-art GMP manufacturing facility to support gene therapy projects emerging from UK universities. GTIMC will also support the development of improved viral vectors, improved yield from the manufacturing process and will also provide essential regulatory and training support. Moreover, the GTIMC hub will allow new training and high-skilled employment opportunities through the ShefVec facility itself, and future start-up companies.

基因疗法依赖于工程病毒载体作为载体，用于递送合成基因，从而允许校正人体多个器官中的疾病改变的变化。在基因治疗方法中利用的病毒已经被修改以去除有害特性并携带感兴趣的治疗基因。目前在研究实验室中进行多种基因治疗方案，使用相对小规模的病毒生产，从而能够优化剂量和给药途径，并在动物疾病模型中测试干预措施的安全性和治疗功效。然而，在英国，生产大量具有一致质量控制GMP等级的临床级病毒所需的设施很少。因此，在进行临床试验之前很容易需要几年时间。目前，现有的设施无法满足学术主导的研究对临床级病毒载体不断增长的需求。这严重阻碍了许多英国资助的世界领先的疾病改善发现转化为临床试验，以造福人类。缺乏合适的GMP设施严重阻碍了开发急需的新型有效治疗方法，用于治疗常规药物化合物无法治疗的多种不治之症。我们建议通过创建一个基因治疗创新和制造中心（GTIMC）来解决制造短缺问题，该中心包括提供一个新的最先进的GMP制造设施，以支持英国大学的基因治疗项目。GTIMC还将支持改进病毒载体的开发，提高生产过程的产量，并提供必要的监管和培训支持。此外，GTIMC中心将通过ShefVec设施本身和未来的初创公司提供新的培训和高技能就业机会。

项目成果

Loss of TMEM106B exacerbates C9ALS/FTD DPR pathology by disrupting autophagosome maturation.

• DOI: 10.3389/fncel.2022.1061559
• 发表时间: 2022
• 期刊: FRONTIERS IN CELLULAR NEUROSCIENCE
• 影响因子: 5.3
• 作者: Bauer, Claudia S.;Webster, Christopher P.;Shaw, Allan C.;Kok, Jannigje R.;Castelli, Lydia M.;Lin, Ya-Hui;Smith, Emma F.;Illanes-Alvarez, Francisco;Higginbottom, Adrian;Shaw, Pamela J.;Azzouz, Mimoun;Ferraiuolo, Laura;Hautbergue, Guillaume M.;Grierson, Andrew J.;De Vos, Kurt J.
• 通讯作者: De Vos, Kurt J.

SPG15 protein deficits are at the crossroads between lysosomal abnormalities, altered lipid metabolism and synaptic dysfunction.

• DOI: 10.1093/hmg/ddac063
• 发表时间: 2022-08-23
• 期刊: Human molecular genetics
• 影响因子: 3.5

SRSF1-dependent inhibition of C9ORF72-repeat RNA nuclear export: genome-wide mechanisms for neuroprotection in amyotrophic lateral sclerosis.

• DOI: 10.1186/s13024-021-00475-y
• 发表时间: 2021-08-10
• 期刊: Molecular neurodegeneration
• 影响因子: 15.1
• 作者: Castelli LM;Cutillo L;Souza CDS;Sanchez-Martinez A;Granata I;Lin YH;Myszczynska MA;Heath PR;Livesey MR;Ning K;Azzouz M;Shaw PJ;Guarracino MR;Whitworth AJ;Ferraiuolo L;Milo M;Hautbergue GM
• 通讯作者: Hautbergue GM

Delivery of therapeutic AAV9 vectors via cisterna magna to treat neurological disorders.

通过小脑延髓池递送治疗性 AAV9 载体以治疗神经系统疾病。

• DOI: 10.1016/j.molmed.2021.09.007
• 发表时间: 2022
• 期刊: Trends in molecular medicine
• 影响因子: 13.6
• 作者: Marchi PM