The NIH Somatic Cell Genome Editing program

Krishanu Saha^#^{1

2

3

4}, Erik J Sontheimer^#⁵, P J Brooks⁶, Melinda R Dwinell⁷, Charles A Gersbach⁸, David R Liu^{9

10

11}, Stephen A Murray¹², Shengdar Q Tsai¹³, Ross C Wilson¹⁴, Daniel G Anderson^{15

16

17}, Aravind Asokan^{8

18}, Jillian F Banfield^{14

19}, Krystof S Bankiewicz²⁰, Gang Bao²¹, Jeff W M Bulte^{22

23}, Nenad Bursac⁸, Jarryd M Campbell²⁴, Daniel F Carlson²⁴, Elliot L Chaikof²⁵, Zheng-Yi Chen^{26

27

28}, R Holland Cheng²⁹, Karl J Clark³⁰, David T Curiel³¹, James E Dahlman³², Benjamin E Deverman³³, Mary E Dickinson³⁴, Jennifer A Doudna^{14

35

36

37

38

39

40}, Stephen C Ekker³⁰, Marina E Emborg^{41

42}, Guoping Feng⁴³, Benjamin S Freedman^{44

45

46

47}, David M Gamm^{48

49}, Guangping Gao⁵⁰, Ionita C Ghiran⁵¹, Peter M Glazer⁵², Shaoqin Gong^{53

54

48}, Jason D Heaney⁵⁵, Jon D Hennebold⁵⁶, John T Hinson⁵⁷, Anastasia Khvorova⁵⁸, Samira Kiani⁵⁹, William R Lagor³⁴, Kit S Lam⁶⁰, Kam W Leong⁶¹, Jon E Levine⁴², Jennifer A Lewis⁶², Cathleen M Lutz¹², Danith H Ly⁶³, Samantha Maragh⁶⁴, Paul B McCray Jr⁶⁵, Todd C McDevitt^{66

67}, Oleg Mirochnitchenko⁶⁸, Ryuji Morizane⁶⁹, Niren Murthy^{14

70}, Randall S Prather⁷¹, John A Ronald⁷², Subhojit Roy⁷³, Sushmita Roy^{53

54

48

74}, Venkata Sabbisetti⁷⁵, W Mark Saltzman⁷⁶, Philip J Santangelo³², David J Segal⁶⁰, Mary Shimoyama⁷⁷, Melissa C Skala^{53

48

78}, Alice F Tarantal^{79

80

81

82}, John C Tilton⁸³, George A Truskey⁸, Moriel Vandsburger⁷⁰, Jonathan K Watts⁵⁸, Kevin D Wells⁷¹, Scot A Wolfe⁸⁴, Qiaobing Xu⁸⁵, Wen Xue⁵⁸, Guohua Yi⁸⁶, Jiangbing Zhou⁸⁷; SCGE Consortium

Affiliations

¹ Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA. ksaha@wisc.edu.
² Department of Medical History & Bioethics, University of Wisconsin-Madison, Madison, WI, USA. ksaha@wisc.edu.
³ Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA. ksaha@wisc.edu.
⁴ McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI, USA. ksaha@wisc.edu.
⁵ RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA. erik.sontheimer@umassmed.edu.
⁶ Office of Rare Diseases Research, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Bethesda, MD, USA.
⁷ Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
⁸ Department of Biomedical Engineering, Duke University, Durham, NC, USA.
⁹ Merkin Institute of Transformative Technologies, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁰ Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
¹¹ Howard Hughes Medical Institute, Cambridge, MA, USA.
¹² The Jackson Laboratory, Bar Harbor, ME, USA.
¹³ Department of Hematology, St Jude Children's Research Hospital, Memphis, TN, USA.
¹⁴ Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
¹⁵ Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
¹⁶ Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
¹⁷ David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology, Cambridge, MA, USA.
¹⁸ Department of Surgery, Duke University School of Medicine, Durham, NC, USA.
¹⁹ Department of Earth and Planetary Sciences, University of California, Berkeley, Berkeley, CA, USA.
²⁰ Department of Neurological Surgery, Ohio State University, Columbus, OH, USA.
²¹ Department of Bioengineering, Rice University, Houston, TX, USA.
²² Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²³ Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²⁴ Recombinetics, Inc, Eagan, MN, USA.
²⁵ Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA.
²⁶ Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, USA.
²⁷ Program in Neuroscience, Harvard Medical School, Boston, MA, USA.
²⁸ Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.
²⁹ Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA, USA.
³⁰ Department of Biochemistry and Molecular Biology, Mayo Clinic Rochester, Rochester, MN, USA.
³¹ Department of Radiation Oncology, Washington University in St Louis, St Louis, MO, USA.
³² Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
³³ Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA.
³⁴ Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA.
³⁵ Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA.
³⁶ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
³⁷ California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA, USA.
³⁸ Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA, USA.
³⁹ Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
⁴⁰ Gladstone Institute of Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA, USA.
⁴¹ Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA.
⁴² Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, USA.
⁴³ McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁴⁴ Division of Nephrology, University of Washington, Seattle, WA, USA.
⁴⁵ Kidney Research Institute, University of Washington, Seattle, WA, USA.
⁴⁶ Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.
⁴⁷ Department of Medicine, University of Washington, Seattle, WA, USA.
⁴⁸ McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI, USA.
⁴⁹ Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, USA.
⁵⁰ Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
⁵¹ Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
⁵² Department of Therapeutic Radiology, Yale University, New Haven, CT, USA.
⁵³ Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA.
⁵⁴ Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA.
⁵⁵ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
⁵⁶ Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.
⁵⁷ Pat and Jim Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, CT, USA.
⁵⁸ RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.
⁵⁹ Pittsburgh Liver Research Center, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
⁶⁰ Department of Biochemistry and Molecular Medicine, University of California, Davis, Davis, CA, USA.
⁶¹ Department of Biomedical Engineering, Columbia University, New York, NY, USA.
⁶² Wyss Institute, Harvard University, Cambridge, MA, USA.
⁶³ Department of Chemistry, Carnegie-Mellon University, Pittsburgh, PA, USA.
⁶⁴ Biomarker and Genomic Sciences Group, National Institute of Standards and Technology, Gaithersburg, MD, USA.
⁶⁵ Department of Pediatrics, University of Iowa, Iowa City, IA, USA.
⁶⁶ Gladstone Institute of Cardiovascular Disease, Gladstone Institutes, San Francisco, CA, USA.
⁶⁷ Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
⁶⁸ Office of Research Infrastructure Programs, Division of Program Coordination, Planning, and Strategic Initiatives, Office of the Director, National Institutes of Health, Bethesda, MD, USA.
⁶⁹ Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁷⁰ Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
⁷¹ Division of Animal Sciences, University of Missouri, Columbia, MO, USA.
⁷² Robarts Research Institute and Department of Medical Biophysics, The University of Western Ontario, London, Ontario, Canada.
⁷³ Department of Pathology, University of California, San Diego, La Jolla, CA, USA.
⁷⁴ Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA.
⁷⁵ Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
⁷⁶ Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
⁷⁷ Department of Biomedical Engineering, Marquette University and Medical College of Wisconsin, Milwaukee, WI, USA.
⁷⁸ Morgridge Institute for Research, Madison, WI, USA.
⁷⁹ Department of Pediatrics, University of California, Davis, Davis, CA, USA.
⁸⁰ Department of Cell Biology and Human Anatomy, University of California, Davis, Davis, CA, USA.
⁸¹ School of Medicine, University of California, Davis, Davis, CA, USA.
⁸² California National Primate Research Center, University of California, Davis, Davis, CA, USA.
⁸³ Department of Nutrition, Case Western Reserve University, Cleveland, OH, USA.
⁸⁴ Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, Worcester, MA, USA.
⁸⁵ Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
⁸⁶ Department of Pulmonary Immunology, University of Texas Health Sciences Center at Tyler, Tyler, TX, USA.
⁸⁷ Department of Neurosurgery, Yale University, New Haven, CT, USA.

^# Contributed equally.

PMID: 33828315
PMCID: PMC8026397
DOI: 10.1038/s41586-021-03191-1

Review

The NIH Somatic Cell Genome Editing program

Krishanu Saha et al. Nature. 2021 Apr.

. 2021 Apr;592(7853):195-204.

doi: 10.1038/s41586-021-03191-1. Epub 2021 Apr 7.

Authors

Affiliations

¹ Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA. ksaha@wisc.edu.
² Department of Medical History & Bioethics, University of Wisconsin-Madison, Madison, WI, USA. ksaha@wisc.edu.
³ Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA. ksaha@wisc.edu.
⁴ McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI, USA. ksaha@wisc.edu.
⁵ RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA. erik.sontheimer@umassmed.edu.
⁶ Office of Rare Diseases Research, National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, Bethesda, MD, USA.
⁷ Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA.
⁸ Department of Biomedical Engineering, Duke University, Durham, NC, USA.
⁹ Merkin Institute of Transformative Technologies, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁰ Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
¹¹ Howard Hughes Medical Institute, Cambridge, MA, USA.
¹² The Jackson Laboratory, Bar Harbor, ME, USA.
¹³ Department of Hematology, St Jude Children's Research Hospital, Memphis, TN, USA.
¹⁴ Innovative Genomics Institute, University of California, Berkeley, Berkeley, CA, USA.
¹⁵ Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
¹⁶ Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
¹⁷ David H. Koch Institute for Integrative Cancer Research at the Massachusetts Institute of Technology, Cambridge, MA, USA.
¹⁸ Department of Surgery, Duke University School of Medicine, Durham, NC, USA.
¹⁹ Department of Earth and Planetary Sciences, University of California, Berkeley, Berkeley, CA, USA.
²⁰ Department of Neurological Surgery, Ohio State University, Columbus, OH, USA.
²¹ Department of Bioengineering, Rice University, Houston, TX, USA.
²² Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²³ Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²⁴ Recombinetics, Inc, Eagan, MN, USA.
²⁵ Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA, USA.
²⁶ Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, USA.
²⁷ Program in Neuroscience, Harvard Medical School, Boston, MA, USA.
²⁸ Eaton-Peabody Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.
²⁹ Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA, USA.
³⁰ Department of Biochemistry and Molecular Biology, Mayo Clinic Rochester, Rochester, MN, USA.
³¹ Department of Radiation Oncology, Washington University in St Louis, St Louis, MO, USA.
³² Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
³³ Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA.
³⁴ Department of Molecular Physiology and Biophysics, Baylor College of Medicine, Houston, TX, USA.
³⁵ Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA.
³⁶ Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
³⁷ California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, Berkeley, CA, USA.
³⁸ Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA, USA.
³⁹ Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
⁴⁰ Gladstone Institute of Data Science and Biotechnology, Gladstone Institutes, San Francisco, CA, USA.
⁴¹ Department of Medical Physics, University of Wisconsin-Madison, Madison, WI, USA.
⁴² Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI, USA.
⁴³ McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
⁴⁴ Division of Nephrology, University of Washington, Seattle, WA, USA.
⁴⁵ Kidney Research Institute, University of Washington, Seattle, WA, USA.
⁴⁶ Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.
⁴⁷ Department of Medicine, University of Washington, Seattle, WA, USA.
⁴⁸ McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, WI, USA.
⁴⁹ Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, USA.
⁵⁰ Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.
⁵¹ Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
⁵² Department of Therapeutic Radiology, Yale University, New Haven, CT, USA.
⁵³ Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA.
⁵⁴ Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI, USA.
⁵⁵ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
⁵⁶ Division of Reproductive and Developmental Sciences, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA.
⁵⁷ Pat and Jim Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, CT, USA.
⁵⁸ RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA, USA.
⁵⁹ Pittsburgh Liver Research Center, Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
⁶⁰ Department of Biochemistry and Molecular Medicine, University of California, Davis, Davis, CA, USA.
⁶¹ Department of Biomedical Engineering, Columbia University, New York, NY, USA.
⁶² Wyss Institute, Harvard University, Cambridge, MA, USA.
⁶³ Department of Chemistry, Carnegie-Mellon University, Pittsburgh, PA, USA.
⁶⁴ Biomarker and Genomic Sciences Group, National Institute of Standards and Technology, Gaithersburg, MD, USA.
⁶⁵ Department of Pediatrics, University of Iowa, Iowa City, IA, USA.
⁶⁶ Gladstone Institute of Cardiovascular Disease, Gladstone Institutes, San Francisco, CA, USA.
⁶⁷ Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
⁶⁸ Office of Research Infrastructure Programs, Division of Program Coordination, Planning, and Strategic Initiatives, Office of the Director, National Institutes of Health, Bethesda, MD, USA.
⁶⁹ Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
⁷⁰ Department of Bioengineering, University of California, Berkeley, Berkeley, CA, USA.
⁷¹ Division of Animal Sciences, University of Missouri, Columbia, MO, USA.
⁷² Robarts Research Institute and Department of Medical Biophysics, The University of Western Ontario, London, Ontario, Canada.
⁷³ Department of Pathology, University of California, San Diego, La Jolla, CA, USA.
⁷⁴ Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA.
⁷⁵ Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
⁷⁶ Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
⁷⁷ Department of Biomedical Engineering, Marquette University and Medical College of Wisconsin, Milwaukee, WI, USA.
⁷⁸ Morgridge Institute for Research, Madison, WI, USA.
⁷⁹ Department of Pediatrics, University of California, Davis, Davis, CA, USA.
⁸⁰ Department of Cell Biology and Human Anatomy, University of California, Davis, Davis, CA, USA.
⁸¹ School of Medicine, University of California, Davis, Davis, CA, USA.
⁸² California National Primate Research Center, University of California, Davis, Davis, CA, USA.
⁸³ Department of Nutrition, Case Western Reserve University, Cleveland, OH, USA.
⁸⁴ Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, Worcester, MA, USA.
⁸⁵ Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
⁸⁶ Department of Pulmonary Immunology, University of Texas Health Sciences Center at Tyler, Tyler, TX, USA.
⁸⁷ Department of Neurosurgery, Yale University, New Haven, CT, USA.

^# Contributed equally.

PMID: 33828315
PMCID: PMC8026397
DOI: 10.1038/s41586-021-03191-1

Abstract

The move from reading to writing the human genome offers new opportunities to improve human health. The United States National Institutes of Health (NIH) Somatic Cell Genome Editing (SCGE) Consortium aims to accelerate the development of safer and more-effective methods to edit the genomes of disease-relevant somatic cells in patients, even in tissues that are difficult to reach. Here we discuss the consortium's plans to develop and benchmark approaches to induce and measure genome modifications, and to define downstream functional consequences of genome editing within human cells. Central to this effort is a rigorous and innovative approach that requires validation of the technology through third-party testing in small and large animals. New genome editors, delivery technologies and methods for tracking edited cells in vivo, as well as newly developed animal models and human biological systems, will be assembled-along with validated datasets-into an SCGE Toolkit, which will be disseminated widely to the biomedical research community. We visualize this toolkit-and the knowledge generated by its applications-as a means to accelerate the clinical development of new therapies for a wide range of conditions.

PubMed Disclaimer

Conflict of interest statement

K.S. receives sponsored research support from Spotlight Therapeutics. E.J.S. is a co-founder and advisor of Intellia Therapeutics. C.A.G. is a co-founder of Tune Therapeutics, Element Genomics and Locus Biosciences, and an advisor to Sarepta Therapeutics, Levo Therapeutics and Iveric Bio. D.R.L. is a co-founder or founder and scientific advisor of Editas Medicine, Pairwise Plants, Beam Therapeutics and Prime Medicine. S.Q.T. is a member of the scientific advisory board of Kromatid, Inc. D.G.A. is a co-founder of CRISPR Therapeutics, Sigilon, Verseau, VasoRx and Orna, and a consultant for Translate Bio and Obsidian Therapeutics. A.A. is a co-founder of StrideBio and TorqueBio, and an advisor to AstraZeneca, Sarepta Therapeutics, Gemini Therapeutics and BridgeBio. J.F.B. is a co-founder of Metagenomi. J.W.M.B. receives research support from NovaDip Biosciences, Philips Healthcare and Weinberg Medical Physics. D.F.C. and J.C. are employees and shareholders in Recombinetics, Inc. J.E.D. is a co-founder of Guide Therapeutics. K.J.C. is a co-founder of Recombinetics, Inc. and LifEngine Technologies. B.E.D. is on the scientific advisory board of Tevard Biosciences. J.A.D. is a co-founder of Caribou Biosciences, Editas Medicine, Scribe Therapeutics, Intellia Therapeutics and Mammoth Biosciences; a scientific advisory board member of Caribou Biosciences, Intellia Therapeutics, eFFECTOR Therapeutics, Scribe Therapeutics, Mammoth Biosciences, Synthego, Algen Biotechnologies, Felix Biosciences and Inari; a Director at Johnson & Johnson; and has research projects sponsored by Biogen, Pfizer, AppleTree Partners and Roche. S.C.E. is co-founder and chief executive officer of LifEngine Technologies, co-founder of LEAH Labs and chief scientific officer of Mettaforge Therapeutics. D.M.G. is a co-founder and chief scientific advisor for Opsis Therapeutics and holds equity in this company, and also receives sponsored research support from Ascidian Therapeutics. G.G. is a scientific co-founder of Voyager Therapeutics, Adrenas Therapeutics and Aspa Therapeutics. P.M.G. is a co-founder of Cybrexa Therapeutics and Delmab Bio and an advisor to pHLIP, Inc. P.B.M. is on the scientific advisory board and receives support for sponsored research from Spirovant Sciences, Inc. S.K. is the chief scientific officer and co-founder of SafeGen Therapeutics. W.M.S. is a co-founder of and receives research support from Stradefy Biosciences. J.K.W. is a consultant for Flagship Pioneering.

Figures

**Fig. 1. Tools for editing the genomes of cells within the body.**
Activities of the SCGE Consortium converge on editing the genome of cells inside the human body. a, Targets of the genome editors (right) range from DNA within the nucleus of a cell to other nucleic acids elsewhere within a cell, such as DNA within the mitochondria (mtDNA) or RNA in the cytoplasm. Targets of epigenomic editors (left) produce targeted alteration of the chromatin structure—including remodelling, modification of the 3D structure and the direct modification of histones or DNA—without editing the DNA or RNA sequence. Approaches to editing cells outside of the body, as well as germline editing in embryos, are not directly supported by the SCGE Consortium, nor are strategies for gene augmentation through the addition of exogenous DNA. b, Interoperable tools assembled into an SCGE Toolkit will be disseminated to accelerate the translation of safe and effective genome-editing therapeutics into the clinic. Tools encompass several categories: newly developed genome editors, delivery technologies, reporter-animal systems, and human biological systems.

**Fig. 2. New genome editors in development.**
Major classes of genome editors include nucleases, base editors (BE), prime editors, PNAs, RNA editors and epigenome editors. The development of new editors involves mining metagenomic datasets and building upon existing editors, in part by tuning them for increased precision and accuracy. DNMT, DNA methyltransferase; Acr, anti-CRISPR protein; RT, reverse transcriptase; DN1S: dominant-negative mutant of tumour suppressor p53-binding protein 1, 53BP1; TALE-fusions, transcription activator-like effector-fusion with nucleases or cytidine deaminases (DddA).

See this image and copyright information in PMC

References

1. High KA, Roncarolo MG. Gene therapy. N. Engl. J. Med. 2019;381:455–464. - PubMed
1. Doudna JA. The promise and challenge of therapeutic genome editing. Nature. 2020;578:229–236. doi: 10.1038/s41586-020-1978-5. - DOI - PMC - PubMed
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The NIH Somatic Cell Genome Editing program

Affiliations

The NIH Somatic Cell Genome Editing program

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

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