Here we describe engineering a pair
of zinc finger nucleases that, when introduced into human T cells, efficiently disrupt cxcr4 by cleavage and error - prone non-homologous DNA end - joining.
But CRISPR has proven so easy and inexpensive that Dana Carroll of the University of Utah, Salt Lake City, who spearheaded the development
of zinc finger nucleases, says it has brought about the «democratization of gene targeting.»
«CRISPR has proven so easy and inexpensive that Dana Carroll of the University of Utah, Salt Lake City, who spearheaded the development
of zinc finger nucleases, [one of its competitors,] says it has brought about the «democratization of gene targeting.
Not exact matches
Announced a worldwide collaboration with Sangamo Therapeutics, Inc. (Sangamo) using Sangamo's
zinc finger nuclease technology platform for the development
of next - generation ex vivo cell therapies in oncology.
These risks and uncertainties include: Gilead's ability to achieve its anticipated full year 2018 financial results; Gilead's ability to sustain growth in revenues for its antiviral and other programs; the risk that private and public payers may be reluctant to provide, or continue to provide, coverage or reimbursement for new products, including Vosevi, Yescarta, Epclusa, Harvoni, Genvoya, Odefsey, Descovy, Biktarvy and Vemlidy ®; austerity measures in European countries that may increase the amount
of discount required on Gilead's products; an increase in discounts, chargebacks and rebates due to ongoing contracts and future negotiations with commercial and government payers; a larger than anticipated shift in payer mix to more highly discounted payer segments and geographic regions and decreases in treatment duration; availability
of funding for state AIDS Drug Assistance Programs (ADAPs); continued fluctuations in ADAP purchases driven by federal and state grant cycles which may not mirror patient demand and may cause fluctuations in Gilead's earnings; market share and price erosion caused by the introduction
of generic versions
of Viread and Truvada, an uncertain global macroeconomic environment; and potential amendments to the Affordable Care Act or other government action that could have the effect
of lowering prices or reducing the number
of insured patients; the possibility
of unfavorable results from clinical trials involving investigational compounds; Gilead's ability to initiate clinical trials in its currently anticipated timeframes; the levels
of inventory held by wholesalers and retailers which may cause fluctuations in Gilead's earnings; Kite's ability to develop and commercialize cell therapies utilizing the
zinc finger nuclease technology platform and realize the benefits
of the Sangamo partnership; Gilead's ability to submit new drug applications for new product candidates in the timelines currently anticipated; Gilead's ability to receive regulatory approvals in a timely manner or at all, for new and current products, including Biktarvy; Gilead's ability to successfully commercialize its products, including Biktarvy; the risk that physicians and patients may not see advantages
of these products over other therapies and may therefore be reluctant to prescribe the products; Gilead's ability to successfully develop its hematology / oncology and inflammation / respiratory programs; safety and efficacy data from clinical studies may not warrant further development
of Gilead's product candidates, including GS - 9620 and Yescarta in combination with Pfizer's utomilumab; Gilead's ability to pay dividends or complete its share repurchase program due to changes in its stock price, corporate or other market conditions; fluctuations in the foreign exchange rate
of the U.S. dollar that may cause an unfavorable foreign currency exchange impact on Gilead's future revenues and pre-tax earnings; and other risks identified from time to time in Gilead's reports filed with the U.S. Securities and Exchange Commission (the SEC).
In recent years several techniques, such as CRISPR / Cas9 or
zinc finger nucleases have been experimented to directly modify the DNA
of plants and animals.
By using engineered
zinc -
finger nucleases (ZFNs) designed to target an integrated reporter and two endogenous rat genes, Immunoglobulin M (IgM) and Rab38, we demonstrate that a single injection
of DNA or messenger RNA encoding ZFNs into the one - cell rat embryo leads to a high frequency
of animals carrying 25 to 100 % disruption at the target locus.
Scientists can select from a variety
of scalpels, including
zinc finger nucleases, TALENs and CRISPR / Cas9.
Talk
of curing AIDS made front - page news last year, in part due to an astonishing new gene - editing technology: lab - engineered proteins called
zinc finger nucleases.
And in another advance, virologist Paula Cannon
of the University
of Southern California used
zinc finger nucleases to create human stem cells that lack CCR5.
Meanwhile, Cellectis announced it now has «an umbrella patent» that its CEO, Andre Choulika, says «covers most
of the gene editing procedures done with a
nuclease,» including those based on CRISPR - Cas 9, TALENs,
zinc fingers, and many meganucleases.
What's more, say the researchers, the cancer - causing effects
of off - target deletions mistakenly created by the V (D) J enzyme need to be considered in designing site - specific enzymes for genome modification such as
zinc -
finger nucleases, TALENS, or CRISPRs.
Last year, researchers targeted and destroyed this gene in the T - cells
of 12 people with HIV using custom - made proteins called
zinc finger nucleases.
The trial is using a form
of DNA scissors called
zinc finger nucleases (ZFNs).
As an approach to inactivating CCR5, we introduced CCR5 - specific
zinc -
finger nucleases into human CD4 + T cells prior to adoptive transfer, but the need to protect cells from virus strains that use CXCR4 (X4) in place
of or in addition to CCR5 (R5X4) remains.
These approaches, which include exotic sounding tools like
zinc finger nucleases and CRISPR / Cas9, differ from more traditional ways reducing the impact
of the HD mutation on cells.
An unbiased genome - wide analysis
of zinc -
finger nuclease specificity.
Zinc finger nuclease mediated knockout
of ADP - dependent glucokinase in cancer cell lines: effects on cell survival and mitochondrial oxidative metabolism.
Working with proteins called
zinc finger nucleases and TALENs, Zhang attempted to edit the genomes
of mammalian cells with a view to engineering them.
The variety
of new tools available for genetic manipulation now include lentiviral - based gene delivery, and gene editing using CRISPR / Cas9,
zinc finger nucleases (ZFNs) or transcription activator - like effector
nucleases (TALENs).
Zinc finger nucleases [1], [2], transcription activator - like effector
nucleases [3], [4] and homing meganucleases [5] have provided powerful tools to induce targeted mutations in the form
of small insertions or deletions derived from DNA break repair
of nonhomologous end joining (NHEJ) or homologous recombination.
Eventually, the team
of Dow and Sangamo scientists showed that it could engineer
zinc finger nucleases that gave a two - for - one deal.
Ultimately this will include the expanding repertoire
of advanced technologies such as clustered regularly interspaced short palindromic repeats (CRISPR), CRISPR - associated protein 9 (Cas9), and
zinc -
finger nucleases (ZFNs)(46) along with the new clinical indications and markets that they address.
Correction
of dystrophin expression in cells from Duchenne muscular dystrophy patients through genomic excision
of exon 51 by
zinc finger nucleases.
Two newer gene - editing methods —
zinc finger nucleases, used since the late 1990s, and TALENs, first described in 2011 — allowed more precise modifications, he says, «but there was a real art and skill required, and only a handful
of labs could do those.»