The Time Is Ripe for Somatic Genome Editing: NIH Program to Strengthen Translation

• Published in: Molecular therapy Vol. 26; no. 3; pp. 671 - 674
• Main Authors: Fehse, Boris, Abramowski-Mock, Ulrike
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.03.2018; Elsevier Limited; American Society of Gene & Cell Therapy
• Subjects: Advantages; Animals; Bacteria; Binding sites; Capital Financing; CCR5 protein; CRISPR; CRISPR-Cas Systems; Deoxyribonucleic acid; DNA; DNA repair; Endonuclease; Enzymes; Gene Editing - methods; Gene therapy; Genome; Genomes; Genomics - methods; Humans; Leukemia; Lymphoma; Medical research; National Institutes of Health (U.S.); Nuclease; Proteins; Transcription Activator-Like Effector Nucleases; Translation; Translational Medical Research - methods; Translational Medical Research - organization & administration; Tumors; United States; United States; United States > US; China
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1016/j.ymthe.2018.02.005

Thankfully, nature has provided us with functional examples of such enzymes, namely type-IIS endonucleases. [...]the task was obvious, although not easy: the DNA binding domain of a type-IIS endonuclease (such as Fok I) had to be replaced with an artificial domain recognizing the sequence of interest. [...]their main benefit was the ease of cloning (based on various elegant strategies, discussed in Schmid-Burgk et al.12) shortening the time from the idea to the protein from several months (for ZFNs) to a few weeks for TALE nucleases (TALENs). [...]since the early 2010s, labs all over the world have been able to develop high-efficiency TALENs for multiple target genes, including therapeutically relevant ones, such as CCR5.13 As a consequence, translation toward the clinics was much faster for TALENs, with the first clinical application appearing in 2015.14 Very soon after, TALENs were pushed aside by the new shooting star, the CRISPR/Cas system.15 Despite its complicated name (CRISPR: clustered regularly interspaced short palindromic repeats; Cas: CRISPR-associated [protein]), this new tool is extremely easy to be applied, which has made all alternative means of genome editing look very old-fashioned. The best indicator for the success of CRISPR/Cas has been the extremely fast distribution into obviously all areas of wet-lab life-technology research. [...]translation into clinical application in somatic gene therapy was even faster than with TALENs. Altogether, this is very timely initiative, which surely will be acclaimed by all researchers in the field. [...]Molecular Therapy, the official flagship journal of the ASGCT, is very happy to support and promote this project.Conflicts of Interest The authors are inventors on a patent for a specific TALEN (CCR5-Uco-TALEN) applied for by the UMC Hamburg-Eppendorf.