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.

项目概要 基因驱动实现了超孟德尔遗传，将基因传递给后代的机会是 100%，这种超孟德尔遗传已在多个工程基因中得到证实 有机体。整个生态系统中基因驱动介导的性状传播可能会用于消除 疾病（例如疟疾、登革热）或入侵物种，并逆转植物的农药抗性。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

A Single-Molecule View of Genome Editing Proteins : Biophysical Mechanisms for TALEs and CRISPR / Cas 9

基因组编辑蛋白的单分子视图：TALE 和 CRISPR/Cas 9 的生物物理机制

• 发表时间: 2024-09-13
• 作者: Thomas M Truskett;Abhirup Mukherjee;D. Schaffer;R. Kane;S. Bent
• 通讯作者: S. Bent

Chemogenetic System Demonstrates That Cas9 Longevity Impacts Genome Editing Outcomes.

化学遗传学系统证明 Cas9 寿命影响基因组编辑结果。

• 发表时间: 2020-12-23
• 影响因子: 18.2
• 作者: Sreekanth, Vedagopuram;Zhou, Qingxuan;Kokkonda, Praveen;Bermudez;Lim, Donghyun;Law, Benjamin K;Holmes, Benjamin R;Chaudhary, Santosh K;Pergu, Rajaiah;Leger, Brittany S;Walker, James A;Gifford, David K;Sherwood, Richard I;Cho
• 通讯作者: Cho