Zinc Finger Nucleases

Genetically engineered nucleases that cleave DNA at a defined distance from specific DNA sequences recognized by ZINC FINGER DNA-BINDING DOMAINS. They are composed of a DNA cleaving domain adapted from DNA endonucleases fused to a zinc finger DNA-binding domain.

Also Known As:

Networked: 111 relevant articles (3 outcomes, 16 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Experts

1.	Holmes, Michael C: 7 articles (03/2017 - 06/2005)
2.	Gregory, Philip D: 7 articles (08/2015 - 06/2005)
3.	Urnov, Fyodor D: 6 articles (03/2017 - 06/2005)
4.	Rebar, Edward J: 5 articles (03/2017 - 07/2011)
5.	Geurts, Aron M: 4 articles (10/2016 - 03/2014)
6.	Ding, Wencheng: 3 articles (01/2020 - 12/2014)
7.	Wang, Hui: 3 articles (01/2020 - 12/2014)
8.	Wang, Liming: 3 articles (01/2020 - 12/2014)
9.	Zhu, Da: 3 articles (01/2020 - 12/2014)
10.	Reik, Andreas: 3 articles (03/2017 - 05/2012)

Related Diseases

1.	Neoplasms (Cancer) 11/01/2017 - "Among all the techniques used, RNAi, zinc finger nucleases and CRISPR hold a brighter future towards creating a Cancer Free World." 08/01/2012 - "In human tumor cells, MALAT1 expression was abrogated using Zinc Finger Nucleases. " 03/01/2013 - "Development of novel cancer therapeutics targeting HR pathways would benefit from a quantitative and rapid means of measuring HR. Here, we describe a zinc finger nuclease (ZFN) assay that can quantify HR. Knockdown of BRCA1 or inactivation of BRCA2 decreased HR activity in cells, whereas gene restoration induced activity 8-fold. " 02/01/2013 - "To uncover its functional importance, we developed a MALAT1 knockout model in human lung tumor cells by genomically integrating RNA destabilizing elements using zinc finger nucleases. " 01/01/2013 - "To better characterize these important cancer related genes, we tagged STAT3 and STAT1 loci with fluorescent protein (FP) sequences (RFP and GFP respectively) by targeted integration via zinc finger nuclease (ZFN)--mediated homologous recombination in A549 cells that express aberrantly activated STAT3. "
2.	Inborn Genetic Diseases (Disease, Hereditary) 03/01/2015 - "Zinc finger nuclease technology: advances and obstacles in modelling and treating genetic disorders." 06/01/2010 - "Gene correction by homologous recombination with zinc finger nucleases in primary cells from a mouse model of a generic recessive genetic disease." 06/01/2020 - "The development of clustered regularly interspaced short palindromic repeats (CRISPR) has spurred a successive wave of genome-engineering following zinc finger nucleases and transcription activator-like effector nucleases, and made gene-editing a promising strategy in the prevention and treatment of genetic diseases. " 10/16/2015 - "Programmable nucleases, such as zinc finger nucleases (ZFNs), transcription activator like effector nucleases (TALENs), and clustered regularly interspersed short palindromic repeats associated protein-9 (CRISPR-Cas9), hold tremendous potential for applications in the clinical setting to treat genetic diseases or prevent infectious diseases. " 04/01/2023 - "Compared to its predecessors, zinc-finger nucleases (ZFN) and transcription activator-like effectors (TALEN), clustered regularly interspaced short palindromic repeats (CRISPR/Cas9) is currently the most efficient molecular tool for genome editing. This system, originally identified as a bacterial adaptive immune system, is capable of cutting and modifying any gene of a large number of living organisms. Numerous trials using this technology are being developed to provide effective treatment for several diseases, such as cancer, cardiovascular and ophthalmic disorders. In research, this technology is increasingly used for genetic disease modelling, providing meaningful models of relevant studies as well as a better understanding of underlying pathological mechanisms. Many molecular tools are now available to put this technique into practice in laboratories, and despite the technical and ethical issues raised by manipulation of the genome, CRIPSR/Cas9 offers a new breath of hope for therapeutic research around the world."
3.	Severe Combined Immunodeficiency (Bare Lymphocyte Syndrome) 06/02/2005 - "We show that zinc-finger nucleases designed against an X-linked severe combined immune deficiency (SCID) mutation in the IL2Rgamma gene yielded more than 18% gene-modified human cells without selection. " 01/01/2018 - "In vitro experiments in DNA-dependent protein kinase catalytic subunit severe combined immunodeficiency (Prkdc scid) fibroblasts using designed zinc finger nucleases (ZFN) and a repair template demonstrated molecular and functional correction of the defect. " 01/25/2010 - "Recently, zinc-finger nucleases (ZFNs) were successfully used to create genome-specific double-stranded breaks and thereby induce targeted gene mutations in a wide variety of organisms including plants, drosophila, zebrafish, etc. We report here on ZFN-induced gene targeting of the rat interleukin 2 receptor gamma (Il2rg) locus, where orthologous human and mouse mutations cause X-linked severe combined immune deficiency (X-SCID). " 05/01/2015 - "In this study, we established zinc-finger nuclease-mediated genome editing in primary fibroblasts and iPSCs generated from a mouse model for radiosensitive severe combined immunodeficiency (RS-SCID), a rare disorder characterized by cellular sensitivity to radiation and the absence of lymphocytes due to impaired DNA-dependent protein kinase (DNA-PK) activity. " 10/01/2018 - "These include (1) the role of follicular T cells in the differentiation of B cells and development of optimal antibody responses; (2) impaired nuclear factor κB subunit 1 signaling in the pathogenesis of common variable immunodeficiency, revealing an association between impaired B-cell maturation and development of inflammatory conditions; (3) autoimmune and inflammatory manifestations in patients with PIDDs in T- and B-cell deficiencies, as well as in neutrophil disorders; (4) newly described gene defects causing PIDDs, including exostosin-like 3 (EXTL3), TNF-α-induced protein 3 (TNFAIP3 [A20]), actin-related protein 2/3 complex-subunit 1B (ARPC1B), v-Rel avian reticuloendotheliosis viral oncogene homolog A (RELA), hypoxia upregulated 1 (HYOU1), BTB domain and CNC homolog 2 (BACH2), CD70, and CD55; (5) use of rapamycin and the phosphoinositide 3-kinase inhibitor leniolisib to reduce autoimmunity and regulate B-cell function in the activated phosphoinositide 3-kinase δ syndrome; (6) improved outcomes in hematopoietic stem cell transplantation for severe combined immunodeficiency (SCID) in the last decade, with an overall 2-year survival of 90% in part caused by early diagnosis through implementation of universal newborn screening; (7) demonstration of the efficacy of lentiviral vector-mediated gene therapy for patients with adenosine deaminase-deficient SCID; (8) the promise of gene editing for PIDDs using CRISPR/Cas9 and zinc finger nuclease technology for SCID and chronic granulomatous disease; and (9) the efficacy of thymus transplantation in Europe, although associated with an unexpected high incidence of autoimmunity. "
4.	Communicable Diseases (Infectious Diseases) 10/16/2015 - "Programmable nucleases, such as zinc finger nucleases (ZFNs), transcription activator like effector nucleases (TALENs), and clustered regularly interspersed short palindromic repeats associated protein-9 (CRISPR-Cas9), hold tremendous potential for applications in the clinical setting to treat genetic diseases or prevent infectious diseases. " 01/01/2021 - "Genome editing technologies, including clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) proteins, zinc-finger nucleases (ZFNs), and transcription activator-like effector nucleases (TALENs), have played essential roles in the study of new treatment for viral infectious diseases in cell lines, animal models, and clinical trials. " 11/27/2022 - "Zinc-finger nucleases (ZFNs), transcription activator- like effector nucleases (TALENs) and CRISPR-Cas9 have been already applied by ex vivo hematopoietic stem cell (HSC) gene therapy in genetic diseases (i.e., Hemoglobinopathies, Fanconi anemia and hereditary Immunodeficiencies) as well as infectious diseases (i.e., HIV), and the recent development of CRISPR-Cas9-based systems using base and prime editors as well as epigenome editors has provided safer tools for gene therapy. "
5.	Chronic Granulomatous Disease 05/26/2011 - "Oxidase-deficient neutrophils from X-linked chronic granulomatous disease iPS cells: functional correction by zinc finger nuclease-mediated safe harbor targeting." 10/01/2018 - "These include (1) the role of follicular T cells in the differentiation of B cells and development of optimal antibody responses; (2) impaired nuclear factor κB subunit 1 signaling in the pathogenesis of common variable immunodeficiency, revealing an association between impaired B-cell maturation and development of inflammatory conditions; (3) autoimmune and inflammatory manifestations in patients with PIDDs in T- and B-cell deficiencies, as well as in neutrophil disorders; (4) newly described gene defects causing PIDDs, including exostosin-like 3 (EXTL3), TNF-α-induced protein 3 (TNFAIP3 [A20]), actin-related protein 2/3 complex-subunit 1B (ARPC1B), v-Rel avian reticuloendotheliosis viral oncogene homolog A (RELA), hypoxia upregulated 1 (HYOU1), BTB domain and CNC homolog 2 (BACH2), CD70, and CD55; (5) use of rapamycin and the phosphoinositide 3-kinase inhibitor leniolisib to reduce autoimmunity and regulate B-cell function in the activated phosphoinositide 3-kinase δ syndrome; (6) improved outcomes in hematopoietic stem cell transplantation for severe combined immunodeficiency (SCID) in the last decade, with an overall 2-year survival of 90% in part caused by early diagnosis through implementation of universal newborn screening; (7) demonstration of the efficacy of lentiviral vector-mediated gene therapy for patients with adenosine deaminase-deficient SCID; (8) the promise of gene editing for PIDDs using CRISPR/Cas9 and zinc finger nuclease technology for SCID and chronic granulomatous disease; and (9) the efficacy of thymus transplantation in Europe, although associated with an unexpected high incidence of autoimmunity. "

Related Drugs and Biologics

1.	Transcription Activator-Like Effector Nucleases
2.	Proteins (Proteins, Gene)
3.	Transcription Activator-Like Effectors
4.	Phosphatidylinositols (Phosphatidylinositol)
5.	Actin-Related Protein 2-3 Complex (Arp2 3 Complex)
6.	Sirolimus (Rapamycin)
7.	Adenosine Deaminase
8.	leniolisib
9.	DNA (Deoxyribonucleic Acid)
10.	CRISPR-Associated Protein 9

Related Therapies and Procedures

1.	Hematopoietic Stem Cell Transplantation
2.	Transplantation
3.	Therapeutics
4.	Cell- and Tissue-Based Therapy (Cell Therapy)
5.	Self Administration (Administration, Self)