Therapeutic genome editing: prospects and challenges

Cox, David Benjamin Turitz; Platt, Randall J.; Zhang, Feng

doi:10.1038/nm.3793

Cited by 1,140 publications

(933 citation statements)

References 140 publications

(147 reference statements)

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“…There is a fluid relationship between genome editing as employed in heritable disease treatment and its use for human enhancement (Ishii 2015;Cox et al 2015). Genetic human enhancement has substantial security implications.…”

Section: Resultsmentioning

confidence: 99%

Ethics Dumping

Schroeder¹,

Cook²,

Hirsch³

et al. 2018

SpringerBriefs in Research and Innovation Governance

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Section: Resultsmentioning

confidence: 99%

Ethics Dumping

Schroeder¹,

Cook²,

Hirsch³

et al. 2018

SpringerBriefs in Research and Innovation Governance

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“…Genome editing itself also holds tremendous potential for treating the underlying genetic causes of certain diseases (Cox et al 2015;Porteus 2015;Maeder and Gersbach 2016). In one of the most successful examples of this to date, ZFN-mediated disruption of the HIV coreceptor CCR5 was used to engineer HIV resistance into both CD4 þ T cells (Perez et al 2008) and CD34 þ hematopoietic stem/progenitor cells (HSPCs) (Holt et al 2010), proving safe and well-tolerated in a phase I clinical trial that infused these gene-modified T cells into individuals with HIV/AIDS (Tebas et al 2014).…”

Section: Therapeutic Genome Editingmentioning

confidence: 99%

Genome-Editing Technologies: Principles and Applications

Gaj

Sirk

Shui

et al. 2016

Cold Spring Harb Perspect Biol

299

142

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Targeted nucleases have provided researchers with the ability to manipulate virtually any genomic sequence, enabling the facile creation of isogenic cell lines and animal models for the study of human disease, and promoting exciting new possibilities for human gene therapy. Here we review three foundational technologies-clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9), transcription activator-like effector nucleases (TALENs), and zinc-finger nucleases (ZFNs). We discuss the engineering advances that facilitated their development and highlight several achievements in genome engineering that were made possible by these tools. We also consider artificial transcription factors, illustrating how this technology can complement targeted nucleases for synthetic biology and gene therapy.

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“…Furthermore, the ability to expand HSCs in culture would greatly boost the development of gene therapy by allowing selection of transducted cells in which the desired gene has been introduced into the appropriate DNA location; this holds the promise for curing a wide variety of human diseases [10]. In particular, the recently developed targeted genome editing techniques including CRISPR/Cas9 technology [24,25] will be greatly benefited by the ability to expand desired manipulated HSCs ex vivo.…”

Section: Why Ex Vivo Expansion Of Hscsmentioning

confidence: 99%

Ex vivo expansion of hematopoietic stem cells

Xie

Zhang

2015

Sci. China Life Sci.

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Ex vivo expansion of hematopoietic stem cells (HSCs) would benefit clinical applications in several aspects, to improve patient survival, utilize cord blood stem cells for adult applications, and selectively propagate stem cell populations after genetic manipulation. In this review we summarize and discuss recent advances in the culture systems of mouse and human HSCs, which include stroma/HSC co-culture, continuous perfusion and fed-batch cultures, and those supplemented with extrinsic ligands, membrane transportable transcription factors, complement components, protein modification enzymes, metabolites, or small molecule chemicals. Some of the expansion systems have been tested in clinical trials. The optimal condition for ex vivo expansion of the primitive and functional human HSCs is still under development. An improved understanding of the mechanisms for HSC cell fate determination and the HSC culture characteristics will guide development of new strategies to overcome difficulties. In the future, development of a combination treatment regimen with agents that enhance self-renewal, block differentiation, and improve homing will be critical. Methods to enhance yields and lower cost during collection and processing should be employed. The employment of an efficient system for ex vivo expansion of HSCs will facilitate the further development of novel strategies for cell and gene therapies including genome editing. ex vivo expansion, hematopoietic stem cells, niche, signal transduction, cord blood, transplantation, SCID-repopulating cell, genome editing, CRISPR/Cas9 Citation:Xie JJ, Zhang CC. Ex vivo expansion of hematopoietic stem cells.

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Therapeutic genome editing: prospects and challenges

Cited by 1,140 publications

References 140 publications

Ethics Dumping

Ethics Dumping

Genome-Editing Technologies: Principles and Applications

Ex vivo expansion of hematopoietic stem cells

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