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年中，病毒基因转移载体的使用迅速扩展，并具有经批准的疗法 以及晚期临床试验正在接受遗传疾病和多种形式的癌症的治疗 通过疫苗预防传染病。向量设计和病毒生产的主要创新 已经针对基于腺病毒，腺病毒的三个最广泛使用的病毒载体系统完成了 相关病毒（AAV）和慢病毒。对于实验室研究者，细胞和分子生物学方法稳定 过表达和敲除细胞和组织中的基因在现代生物医学中已经是必不可少的 研究。慢病毒介导的过表达和定期间隔短的短质体重复序列 （CRISPR）淘汰技术由于其效率和感染能力而特别强大 分裂和非分散细胞。考虑到使用这些病毒基因转移的大量需求和需求 在罗德岛和其他新英格兰南部地区的技术和缺乏专家服务提供商， 我们提出了一个干细胞和老化（SCA）的慢病毒构造核心（SCA）cobre第3期。我们的长期 目标是向更大的生物医学研究界提供尖端的病毒基因转移技术 罗德岛及以后。为了实现这一目标，我们提出以下4个特定目标：特定目标1。 提供慢病毒技术，以方便访问和有效使用。具体目标2。增强 罗德岛调查人员确保联邦研究资金的竞争力。特定目的3。使我们对齐 核心转化研究。特定目标4。成为一项独立的自我维持服务研究 设施。创新和影响：重组病毒向量是细胞，动物的强大基因输送工具 模型和临床应用。来自我们核心的慢病毒结构在适合不同的适用性上会有所不同 应用程序，并将允许调查人员监视细胞功能，替换，纠正，表达或阻止表达式 靶基因，标记细胞的命运确定，并改变特定细胞群体的生理状态。 Covid-19-Pseudovirus变体的及时发展是创新的一个典型例子。到 遗传工程师的溶瘤腺病毒编码双特异性T细胞探索者是尖端的，而新颖的 免疫疗法有可能对癌症治疗产生深远影响。当前指数 使用AAV载体的临床试验的增长表明，我们仅在开始时就可以实现 AAV是基因疗法的领先平台。这些创新可能会解决具有的疾病 没有其他治疗选择。在这种情况下，慢病毒构造核心已经成功制作了 继续对基本和转化研究的催化剂产生积极影响，以改善人类健康。