招聘简介：
美国国立卫生研究院资助的博士后职位可在哈佛医学院/马萨诸塞州眼耳医院的郑一辰博士的实验室中获得，研究CRISPR/CAS9介导基因编辑治疗遗传性耳聋的开发和应用。
我们有兴趣将CRISPR/CAS9介导的基因组开发成新的基因治疗范式，用于从动物模型到人类患者的遗传性听力损失。我们是第一个展示Crispr编辑剂（以RNP的形式存在的CAS9蛋白和SGRNA，核糖核酸蛋白）能有效地传递到哺乳动物毛细胞中，从而产生高效编辑（Nat Biotech）。zuris等人，2014年）。我们已经证明，RNP提供编辑代理挽救了人类显性耳聋小鼠模型的听力（Nature，Gao等人，2018）。我们的主要目标是开发针对听力损失的基因组编辑疗法，特别关注以下领域：1）。发展编辑技术，提高编辑效率和编辑专一性；开发新的运载工具，包括纳米脂质体，用于RNP运载编辑机械，以针对不同的体细胞；就地检测编辑事件；4）。内切酶生物工程提高活性；利用人类患者的iPS细胞改进CRISPR以纠正疾病表型；在大型动物模型（包括猪和7）中实现高效、准确的编辑。开发新的编辑工具，针对同一耳聋基因的不同突变。
英文原文：
NIH funded postdoctoral positions are available in the laboratory of Dr. Zheng-Yi Chen of Harvard Medical School/Massachusetts Eye & Ear Infirmary on the development and application of CRISPR/Cas9-mediated gene editing to treat genetic deafness.
We are interested in developing CRISPR/Cas9-mediated genome into new gene therapy paradigm for genetic hearing loss from animal models to human patients. We are the first to show CRISPR editing agents (Cas9 protein and sgRNAs in the form of RNP, ribonucleotide proteins) can be efficiently delivered into mammalian hair cells resulting in high efficiency editing (Nat Biotech. Zuris et al2014). We have demonstrated that RNP delivery of editing agents rescued hearing in a mouse model of human dominant deafness (Nature, Gao et al., 2018). Our main focus is to develop genome editing therapy for hearing loss with particular interests in the following areas: 1). Development of editing technology to improve editing efficiency and specificity in vivo; 2). Developing new delivery vehicles including nanoparticle based liposomes for RNP delivery of editing machinery to target diverse somatic cells; 3). Detection of editing events in situ; 4). Bioengineering of endonucleases to improve activity; 5). Advance CRISPR to correct disease phenotype using iPS cells from human patients; 6). Achieve efficient and accurate editing in large animal models including pig and 7). Develop new editing tools to target different mutations in the same deafness gene.
The positions offer unique and exciting opportunities to engaging in developing cutting-edge CRISPR technology for inner ear application with direct implication in humans. The fellows will have the opportunity to conduct the development of CRISPR technology for hearing rescue in animal models in Boston and conduct pig model study in China. The project involves collaboration with Dr. Qiaobing Xu of Tufts University and Dr. David Liu of Broad Institute. We provide an interdisciplinary and collaborative environment in all aspects of hearing research. A successful candidate (Ph.D, M.D/Ph.D or MD) should have a strong background in genome editing technology, genetics, molecular biology and strong interest in application of editing technology to treat human diseases.
Please email a curriculum vita, a description of research accomplishments and names of three references to:
Zheng-Yi Chen, D.Phil. (617-909-6090)
Associate Professor
Harvard Medical School
Massachusetts Eye & Ear Infirmary
Zheng-Yi_Chen@meei.harvard.edu
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