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A zinc finger is a small protein structural motif that is characterized by the coordination of one or more zinc ions (Zn2+) in order to stabilize the fold. It was originally coined to describe the finger-like appearance of a hypothesized structure from the African clawed frog (Xenopus laevis) transcription factor IIIA. However, it has been found to encompass a wide variety of differing protein structures in eukaryotic cells. Xenopus laevis TFIIIA was originally demonstrated to contain zinc and require the metal for function in 1983, the first such reported zinc requirement for a gene regulatory protein followed soon thereafter by the Krüppel factor in Drosophila. It often appears as a metal-binding domain in multi-domain proteins.
A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one structural motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence or have a general affinity to DNA. Some DNA-binding domains may also include nucleic acids in their folded structure.
Therapeutic gene modulation refers to the practice of altering the expression of a gene at one of various stages, with a view to alleviate some form of ailment. It differs from gene therapy in that gene modulation seeks to alter the expression of an endogenous gene whereas gene therapy concerns the introduction of a gene whose product aids the recipient directly.
Zinc-finger nucleases (ZFNs) are artificial restriction enzymes generated by fusing a zinc finger DNA-binding domain to a DNA-cleavage domain. Zinc finger domains can be engineered to target specific desired DNA sequences and this enables zinc-finger nucleases to target unique sequences within complex genomes. By taking advantage of endogenous DNA repair machinery, these reagents can be used to precisely alter the genomes of higher organisms. Alongside CRISPR/Cas9 and TALEN, ZFN is a prominent tool in the field of genome editing.
Artificial transcription factors (ATFs) are engineered individual or multi molecule transcription factors that either activate or repress gene transcription (biology).
The restriction endonuclease Fok1, naturally found in Flavobacterium okeanokoites, is a bacterial type IIS restriction endonuclease consisting of an N-terminal DNA-binding domain and a non-specific DNA cleavage domain at the C-terminal. Once the protein is bound to duplex DNA via its DNA-binding domain at the 5'-GGATG-3' recognition site, the DNA cleavage domain is activated and cleaves, without further sequence specificity, the first strand 9 nucleotides downstream and the second strand 13 nucleotides upstream of the nearest nucleotide of the recognition site.
Jeremy Mark Berg was founding director of the University of Pittsburgh Institute for Personalized Medicine. He holds positions as Associate Senior Vice Chancellor for Science Strategy and Planning and Professor of Computational and Systems Biology at the University of Pittsburgh. From 2016 - 2019, Berg was editor in chief of the Science journals.
Zinc finger protein chimera are chimeric proteins composed of a DNA-binding zinc finger protein domain and another domain through which the protein exerts its effect. The effector domain may be a transcriptional activator (A) or repressor (R), a methylation domain (M) or a nuclease (N).
Nuvelo Inc. was a biopharmaceutical company engaged in the discovery, development and commercialization of drugs for acute cardiovascular disease, cancer and other debilitating medical conditions. On January 27, 2009, the company was acquired by ARCA Biopharma, Inc. in a reverse takeover transaction.
Antibody Solutions is a privately held American contract research organization headquartered in Santa Clara, California. It provides research and discovery services and fit-for-purpose antibodies to biopharmaceutical and diagnostic companies and academic researchers worldwide. The company’s services include monoclonal and polyclonal antibody and antigen development, molecular modeling, antibody sequencing and engineering, bioreactor technology, pharmacokinetic studies, antibody epitope binning, peptide synthesis, immunoassay development, ligand-binding assay analysis, and support for CAR-T research.
Transcription activator-like effector nucleases (TALEN) are restriction enzymes that can be engineered to cut specific sequences of DNA. They are made by fusing a TAL effector DNA-binding domain to a DNA cleavage domain. Transcription activator-like effectors (TALEs) can be engineered to bind to practically any desired DNA sequence, so when combined with a nuclease, DNA can be cut at specific locations. The restriction enzymes can be introduced into cells, for use in gene editing or for genome editing in situ, a technique known as genome editing with engineered nucleases. Alongside zinc finger nucleases and CRISPR/Cas9, TALEN is a prominent tool in the field of genome editing.
Genome editing, or genome engineering, or gene editing, is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. Unlike early genetic engineering techniques that randomly inserts genetic material into a host genome, genome editing targets the insertions to site-specific locations. The basic mechanism involved in genetic manipulations through programmable nucleases is the recognition of target genomic loci and binding of effector DNA-binding domain (DBD), double-strand breaks (DSBs) in target DNA by the restriction endonucleases, and the repair of DSBs through homology-directed recombination (HDR) or non-homologous end joining (NHEJ).
Richard H. Scheller is the former Chief Science Officer and Head of Therapeutics at 23andMe and the former Executive Vice President of Research and Early Development at Genentech. He was a professor at Stanford University from 1982 to 2001 before joining Genentech. He has been awarded the Alan T. Waterman Award in 1989, the W. Alden Spencer Award in 1993 and the NAS Award in Molecular Biology in 1997, won the 2010 Kavli Prize in Neuroscience with Thomas C. Südhof and James E. Rothman, and won the 2013 Albert Lasker Award for Basic Medical Research with Thomas Südhof. He was also given the Life Sciences Distinguished Alumni Award from University of Wisconsin–Madison. He is a Fellow of the American Academy of Arts and Sciences and a Member of the National Academy of Sciences.
Stephen Philip Jackson, FRS, FMedSci, is the Frederick James Quick Professor of Biology. He is a Senior Group Leader and Head of Cancer Research UK Laboratories at the Gurdon Institute.
Andreas Plückthun is a scientist whose research is focused on the field of protein engineering. Andreas Plückthun is the director of the department of biochemistry at the University of Zurich. Plückthun was appointed to the faculty of the University of Zurich as a Full professor of biochemistry in 1993. Plückthun was group leader at the Max Planck Institute of Biochemistry, Germany (1985-1993). He was elected to the European Molecular Biology Organization (EMBO) in 1992, and named a member of the German National Academy of Science (Leopoldina) in 2003. He is cofounder of the biotechnology companies Morphosys Molecular Partners AG and G7 Therapeutics..
Since antiretroviral therapy requires a lifelong treatment regimen, research to find more permanent cures for HIV infection is currently underway. It is possible to synthesize zinc finger nucleotides with zinc finger components that selectively bind to specific portions of DNA. Conceptually, targeting and editing could focus on host cellular co-receptors for HIV or on proviral HIV DNA.
Sangamo Therapeutics, Inc. is an American biotechnology company based in Brisbane, California. It applies cell and gene therapy to combat haemophilia and other genetic diseases.
Carlos F. Barbas III was chair professor of the Janet and Keith Kellogg II and a chemist at the Scripps Research Institute. Barbas developed new therapies that can target HIV-1 and some kinds of cancer which went into clinical trials.
Alan Edward Smith is a British geneticist who was Chief Scientific Officer of Genzyme from 1996 to 2011.
Fyodor Dmitriyevich Urnov is Russian-born biomedical researcher and who has played a leading role in the field of genome editing. He is a Professor of Genetics, Genomics, and Development at the University of California, Berkeley and Director of the Center for Translational Genomics at the university's Innovative Genomics Institute. In 2005 Urnov and his colleagues coined the term "genome editing" and demonstrated the first use of ZFNs to edit DNA in human cells. Urnov is considered a pioneering figure in the field of genome editing and his work has been cited widely.
References
- ↑ Rebar, Edward John (1997). Selection studies of zinc finger-DNA recognition (Thesis). OCLC 37525775.
- 1 2 "Sangamo Therapeutics appoints Edward Rebar as senior vice president". Post Online Media. Richmond, California. July 16, 2018. Retrieved October 1, 2018.
- ↑ Hale, Conor (July 20, 2018). "Chutes & Ladders: Sangamo loses another top executive". FierceBiotech. Retrieved February 11, 2019.
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