Lentivirus Construct Core

慢病毒构建核心

• 批准号: 10630391
• 负责人: OLIN D. Liang
• 金额: $ 21.32万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10630391
• 关键词: 2019-nCoV; Address; Adenoviruses; Adoption; Aging; Animal Model; Basic Science; Biology; Biomedical Research; COVID-19; COVID-19 pandemic; Caliber; Cancer Center; Cardiovascular system; Cell physiology; Cells; Cellular biology; Centers of Research Excellence; Clinical Trials; Clustered Regularly Interspaced Short Palindromic Repeats; Collaborations; Communicable Diseases; Communities; Country; Data; Dependovirus; Development; Disease; Faculty; Fees; Funding; Gene Delivery; Gene Transduction Agent; Genes; Genetic Diseases; Genetic Engineering; Goals; Grant; Growth; Health; Health Services Research; Hematologic Neoplasms; Hospitals; Human; Infrastructure; Institution; Interphase Cell; K-Series Research Career Programs; Knock-out; Laboratories; Lentivirus; Malignant Neoplasms; Mediating; Medical center; Methods; Modernization; Molecular Biology; Monitor; Neurosciences; New England; Orthopedics; Pathogenesis; Phase; Physicians; Physiological; Population; Prevention; Production; Research; Research Activity; Research Personnel; Rest; Rhode Island; Role; Scientist; Secure; Series; Services; Solid Neoplasm; Strategic Planning; System; Techniques; Technology; Technology Transfer; Tissues; Translational Research; United States National Institutes of Health; Universities; Vaccination; Variant; Veins; Viral; Viral Genes; Viral Vector; Virus; adeno-associated viral vector; bi-specific T cell engager; cancer therapy; catalyst; clinical application; cost; design; diagnostic tool; experimental study; gene therapy; gene transfer vector; immunotherapeutic virotherapy; improved; innovation; interest; laboratory equipment; medical schools; meetings; member; novel; novel diagnostics; novel therapeutics; oncolytic adenovirus; overexpression; recombinant viral vector; research facility; service providers; sound; stem cells; tool; translational research program; vector

Project Summary/Abstract: The past 20 years have seen a rapid expansion in the use of viral gene transfer vectors, with approved therapies and late stage clinical trials underway for the treatment of genetic disorders and multiple forms of cancer, as well as prevention of infectious diseases through vaccination. Major innovations in vector design and virus production have been accomplished for the three most widely used viral vector systems based on adenovirus, adeno- associated virus (AAV), and lentivirus. For laboratory investigators, cell and molecular biology methods to stably over-express and knockout a gene in cells and tissues have become indispensable in modern biomedical research. Lentivirus-mediated over-expression and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) knockout techniques are particularly powerful due to their efficiency and the capability of infecting dividing and non-dividing cells. Given the significant need and demand to use these viral gene transfer technologies and the lack of expert service providers in Rhode Island and the rest Southern New England region, we propose a Lentivirus Construct Core for the Stem Cells and Aging (SCA) COBRE Phase 3. Our long-term goal is to provide cutting-edge viral gene transfer technologies to the greater biomedical research community in Rhode Island and beyond. To accomplish this goal, we propose the following 4 Specific Aims: Specific Aim 1. To provide lentivirus technologies for easy access and efficient use. Specific Aim 2. To enhance the competitiveness of Rhode Island investigators to secure federal research funding. Specific Aim 3. To align our Core with translational research. Specific Aim 4. To become an independent self-sustainable service research facility. Innovations and impact: Recombinant viral vectors are powerful gene delivery tools for cells, animal models, and clinical applications. The lentiviral constructs from our Core will differ in their suitability for different applications, and will allow investigators to monitor cell functions, replace, correct, express or block expression of target genes, tag cells for fate determination, and change the physiological state of specific cell populations. The timely development of COVID-19 pseudovirus variants by our Core was a prime example of innovation. To genetically engineer oncolytic adenovirus encoding bispecific T cell engagers is cutting-edge, and the novel immunovirotherapies have the potential to make a profound impact in cancer treatments. The current exponential growth of clinical trials using AAV vectors suggests that we are only at the beginning of what is achievable for AAV as the leading platform for gene therapies. These innovations can potentially address diseases that have no other treatment options. In this vein, the Lentivirus Construct Core has already successfully made and will continue to make a positive impact as a catalyst on basic and translational research to improve human health.

项目摘要/摘要： 在过去的20年里，病毒基因转移载体的使用迅速扩大，并获得了批准的治疗方法 治疗遗传性疾病和多种癌症的晚期临床试验也在进行中 通过接种疫苗来预防传染病。媒介设计和病毒生产的主要创新 已经完成了基于腺病毒、腺病毒和重组腺病毒的三种最广泛使用的病毒载体系统。 相关病毒(AAV)和慢病毒。对于实验室研究人员来说，细胞和分子生物学方法能够稳定地 在细胞和组织中过度表达和敲除基因已成为现代生物医学中不可缺少的 研究。慢病毒介导的过度表达与有规律间隔的短回文重复序列 (CRISPR)基因敲除技术因其效率和感染能力而特别强大 分割和非分割单元格。考虑到使用这些病毒基因转移的巨大需求和需求 罗德岛和新英格兰南部其他地区的技术和缺乏专家服务提供商， 我们建议为干细胞和衰老(SCA)Cobre阶段3构建慢病毒核心。我们的长期 目标是为更广泛的生物医学研究社区提供尖端的病毒基因转移技术 罗德岛和更远的地方。为了实现这一目标，我们提出了以下4个具体目标：具体目标1。 提供慢病毒技术，便于访问和高效使用。具体目标2.加强 罗德岛调查人员获得联邦研究资金的竞争力。具体目标3.使我们的 以翻译研究为核心。具体目标4.成为独立、自给自足的服务研究机构 设施。创新和影响：重组病毒载体是细胞和动物的强大基因传递工具 模型和临床应用。来自我们核心的慢病毒结构将在它们对不同的 应用程序，并将允许调查人员监测细胞功能，替换、纠正、表达或阻断表达 目标基因，标记细胞以决定命运，并改变特定细胞群体的生理状态。 我们的核心及时开发出新冠肺炎伪病毒变体就是一个很好的创新例子。至 基因工程编码双特异性T细胞活塞子的溶瘤腺病毒是最先进的，而且新的 免疫病毒疗法有可能对癌症治疗产生深远影响。当前的指数 使用AAV载体的临床试验的增长表明，我们只是处于可以实现的目标的开始 AAV作为基因治疗的领先平台。这些创新可以潜在地解决 没有其他治疗选择。在这种情况下，慢病毒构建核心已经成功地制作了，并将 继续对基础研究和转化研究产生积极影响，以改善人类健康。