Development of synthetic gene drives using small molecules

使用小分子开发合成基因驱动器

• 批准号: 10470220
• 负责人: Omar Sultan Akbari
• 金额: $ 35.73万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10470220
• 关键词: Acute; Adverse effects; Alleles; Animal Husbandry; Biomedical Technology; Bypass; CRISPR/Cas technology; Chemistry; Clustered Regularly Interspaced Short Palindromic Repeats; Complex; Computer Models; Country; Dengue Fever; Development; Disease; Dose; Drosophila genus; Ecosystem; Endemic Diseases; Engineered Gene; Engineering; Environment; Food; Foundations; Gene Activation; Genes; Genetic; Genetic Engineering; Guide RNA; Heterogeneity; Heterozygote; Homozygote; India; Investigation; Laboratories; Lethal Genes; Malaria; Mediating; Methodology; Methods; Modeling; Mosaicism; Organism; Output; Parasites; Parents; Plants; Population; Population Control; Population Dynamics; Prodrugs; Streptococcus pyogenes; Synthetic Genes; System; Technology; Time; Trimethoprim; Ubiquitination; Vector-transmitted infectious disease; base; computer studies; gene drive system; inhibitor; insight; mathematical model; microbiome; mimicry; multicatalytic endopeptidase complex; next generation; nuclease; pesticide resistance; repaired; screening; small molecule; small molecule inhibitor; tool; trait; ubiquitin ligase; vector control

PROJECT SUMMARY Gene drives enable a super-Mendelian inheritance where the chance of passing on the gene to the progeny is 100%, and this super-Mendelian inheritance has been demonstrated for several engineered genes in multiple organisms. Gene-drive mediated trait propagation in the entire ecosystem may find use in the elimination of diseases (e.g., malaria, dengue fever) or invasive species, and reversing the pesticide resistance in plants. We propose to use tools and principles of chemistry to develop controllers that will allow us to understand the strength and limitations of the gene drive technologies.

项目总结 基因驱动实现了超级孟德尔式遗传，将基因传递给后代的机会是 100%，而且这种超级孟德尔遗传已经被证明在多个 有机体。在整个生态系统中，基因驱动介导的性状繁殖可能会在消除 疾病(如疟疾、登革热)或入侵物种，以及扭转植物对杀虫剂的抗药性。我们 建议使用化学工具和原理来开发控制器，使我们能够理解 基因驱动技术的优势和局限性。

项目成果

Chemogenetic System Demonstrates That Cas9 Longevity Impacts Genome Editing Outcomes.

• DOI: 10.1021/acscentsci.0c00129
• 发表时间: 2020-12-23
• 期刊: ACS central science
• 影响因子: 18.2
• 作者: Sreekanth V;Zhou Q;Kokkonda P;Bermudez-Cabrera HC;Lim D;Law BK;Holmes BR;Chaudhary SK;Pergu R;Leger BS;Walker JA;Gifford DK;Sherwood RI;Choudhary A
• 通讯作者: Choudhary A

Chemical and optical control of CRISPR-associated nucleases.

• DOI: 10.1016/j.cbpa.2020.10.003
• 发表时间: 2021-02-01
• 期刊: Current opinion in chemical biology
• 影响因子: 7.8
• 作者: Modell, Ashley E;Siriwardena, Sachini U;Choudhary, Amit
• 通讯作者: Choudhary, Amit