201. Gene editing and CRISPR in the clinic: current and future perspectives
- Author
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Jerilyn A. Timlin, Matthew P. Hirakawa, Kimberly S. Butler, James P. Carney, and Raga Krishnakumar
- Subjects
0301 basic medicine ,gene activation ,Genetic Vectors ,Biophysics ,Cell Culture Techniques ,Computational biology ,Biology ,Biochemistry ,Immunotherapy, Adoptive ,DNA sequencing ,Molecular Bases of Health & Disease ,Translational Research, Biomedical ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Drug Delivery Systems ,Genome editing ,Transcription Activator-Like Effector Nucleases ,CRISPR ,genome editing ,Animals ,Humans ,Molecular Biology ,Review Articles ,Gene Editing ,Transcription activator-like effector nuclease ,Clinical Trials as Topic ,Receptors, Chimeric Antigen ,Cas9 ,Effector ,clinical trial ,Cell Biology ,Genomics ,Genetic Therapy ,Zinc finger nuclease ,zinc finger nuclease ,Zinc Finger Nucleases ,030104 developmental biology ,030220 oncology & carcinogenesis ,Models, Animal ,Nanoparticles ,CRISPR-Cas Systems ,Biotechnology - Abstract
Genome editing technologies, particularly those based on zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR (clustered regularly interspaced short palindromic repeat DNA sequences)/Cas9 are rapidly progressing into clinical trials. Most clinical use of CRISPR to date has focused on ex vivo gene editing of cells followed by their re-introduction back into the patient. The ex vivo editing approach is highly effective for many disease states, including cancers and sickle cell disease, but ideally genome editing would also be applied to diseases which require cell modification in vivo. However, in vivo use of CRISPR technologies can be confounded by problems such as off-target editing, inefficient or off-target delivery, and stimulation of counterproductive immune responses. Current research addressing these issues may provide new opportunities for use of CRISPR in the clinical space. In this review, we examine the current status and scientific basis of clinical trials featuring ZFNs, TALENs, and CRISPR-based genome editing, the known limitations of CRISPR use in humans, and the rapidly developing CRISPR engineering space that should lay the groundwork for further translation to clinical application.
- Published
- 2020