SpongeBot: genetically engineered cells to suppress SARS-CoV-2 and future viruses

SpongeBot：基因工程细胞抑制 SARS-CoV-2 和未来病毒

• 批准号: 10186867
• 负责人: Darrell J Irvine
• 金额: $ 75.24万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-19 至 2022-12-18
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10186867
• 关键词: 2019-nCoV; ACE2; Adaptive Immune System; Address; Animal Model; Antibodies; Antibody-Dependent Enhancement; Antiviral Agents; Appearance; Attenuated; Biodistribution; Biological Assay; Biomedical Engineering; COVID-19; COVID-19 mortality; COVID-19 pandemic; COVID-19 patient; Capsid; Cell Therapy; Cell membrane; Cells; Cellular biology; Cessation of life; Chimeric Proteins; Clinical; Clinical Research; Clinical Trials; Complex; Conserved Sequence; Custom; Dangerousness; Dengue; Dengue Virus; Development; Disease; Distant; Ebola; Economics; Elderly; Epithelial Cells; Future; Genes; Genetic Engineering; Genome; Genomics; Grant; Guide RNA; HIV; Health; Health Personnel; Human; Human Characteristics; IL4 gene; Immune response; Immune system; Immunocompromised Host; Immunology; In Vitro; Individual; Infection; Inflammation; Inflammatory; Injury; Innate Immune System; Interleukin 6 Receptor; Interleukin-10; Kinetics; Lead; Libraries; Lung; Measures; Mesenchymal Stem Cells; MicroRNAs; Middle East Respiratory Syndrome; Molecular; Molecular Biology; Mus; Mutation; National Institute of Biomedical Imaging and Bioengineering; Organ; Pathogenicity; Peptide Hydrolases; Pharmaceutical Preparations; Placenta; Play; Populations at Risk; Proteins; RNA; Rattus; SARS coronavirus; SARS-CoV-2 infection; SARS-CoV-2 spike protein; Safety; Site; Source; System; Systems Biology; TMPRSS2 gene; Technology; Testing; Therapeutic; Time; TimeLine; Tissues; Treatment Efficacy; United States National Institutes of Health; Vaccination; Vaccines; Viral; Viral Genome; Viral Load result; Virion; Virulent; Virus; Virus Diseases; Vulnerable Populations; attenuation; authority; base; cellular engineering; cytokine; cytokine release syndrome; cytotoxicity; design; drug repurposing; genetic element; genetically modified cells; immunoregulation; in vivo; indexing; mortality; mutant; neutralizing antibody; novel; novel virus; overexpression; pandemic disease; particle; pathogen; prevent; prophylactic; response; safety testing; synthetic biology; vaccine-induced antibodies; viral DNA; viral RNA; virology

SpongeBot represents a new class of genetically modified cells to address the COVID-19 pandemic, leveraging a novel antiviral platform developed under the proposer team’s existing NIH NIBIB R01 project. This antiviral platform facilitates rapid, targeted SpongeBot development and deployment against SARS-CoV-2, its viral mutations, as well as entirely new viruses - providing a barrier to future viral pandemics. SARS-CoV-2 is highly communicable and individuals can transmit the disease even prior to becoming symptomatic, sharply increasing the rate of disease spread. During the first two weeks following infection, the innate immune system attempts to slow down the rapidly multiplying pathogen to provide time for the adaptive immune system to develop more specific and effective mechanisms to destroy the virus. However, in individuals with decreased or compromised immune responses, the excessive viral load can lead to elevated inflammation, severe tissue damage, and ultimately death. SpongeBot, our bioengineered cell-based therapy solution, provides vital support to the body’s immune system, through its genetically designed ability to sequester and destroy SARS-CoV-2 viral particles at sites of injury, in addition to attenuation of the immune system’s hyperinflammatory response to the virus. Administering SpongeBot cells to an infected individual reduces and keeps viral load below dangerous thresholds, prevents harmful hyperinflammation, and provides the adaptive immune system the time required to mount an effective defense against the virus. SpongeBot can be administered prophylactically to at-risk populations (e.g., healthcare workers, the elderly, or immunocompromised individuals), or therapeutically at any stage during the course of viral infection. Importantly, SpongeBot therapy is extremely safe; the base technology has a long proven clinical safety track record. Unlike the lengthy development times necessary for vaccines or antiviral medications, a targeted SpongeBot therapy against a predicted virus can be placed in clinical trials immediately. SpongeBot development for a novel virus would be ready for deployment in only about 12 weeks.

SpongeBot代表了一类新的转基因细胞，以应对COVID-19大流行，利用 一种新的抗病毒平台，是在提议者团队现有的NIH NIBIB R 01项目下开发的。这种抗病毒药物 该平台促进了针对SARS-CoV-2的快速、有针对性的SpongeBot开发和部署， 突变，以及全新的病毒-为未来的病毒大流行提供了屏障。 SARS-CoV-2具有高度传染性，个体甚至在成为 症状，急剧增加疾病传播的速度。在感染后的前两周， 先天免疫系统试图减缓快速繁殖的病原体，为适应性免疫提供时间。 免疫系统发展更具体和有效的机制来摧毁病毒。然而，在个人 随着免疫应答的降低或受损，过量的病毒载量可导致炎症升高， 严重的组织损伤最终导致死亡 SpongeBot是我们的生物工程细胞治疗解决方案，为人体免疫系统提供重要支持， 通过其基因设计的能力，在损伤部位隔离和破坏SARS-CoV-2病毒颗粒， 此外，还能减弱免疫系统对病毒的高度炎症反应。施用 SpongeBot细胞对受感染的个体减少并保持病毒载量低于危险阈值， 有害的过度炎症，并提供适应性免疫系统所需的时间来安装有效的 防御病毒。 SpongeBot可以对高危人群（例如，医护人员、老年人或 免疫功能低下的个体），或在病毒感染过程中的任何阶段进行治疗。重要的是， SpongeBot疗法非常安全;基础技术具有长期的临床安全记录。不像 疫苗或抗病毒药物、有针对性的SpongeBot疗法所需的漫长开发时间 可以立即投入临床试验。SpongeBot开发一种新型病毒 只需要12周就可以部署

项目成果

PERSIST platform provides programmable RNA regulation using CRISPR endoRNases.

• DOI: 10.1038/s41467-022-30172-3
• 发表时间: 2022-05-11
• 期刊: Nature communications
• 影响因子: 16.6