ArticleProceedings of the National Academy of Sciences of the United States of America1999
Toward controlling gene expression at will: selection and design of zinc finger domains recognizing each of the 5'-GNN-3' DNA target sequences.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 162 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
162 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The past, present, and future of artificial zinc finger proteins: design strategies and chemical and biological applications.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2023Pooled it
- Epigenetic editing approaches maturity: AI-driven precision design, delivery innovation, and the road to clinical translation.Clinical epigenetics · 2026Review
- Gene therapy for huntington's disease: advances, challenges, and future perspectives.Neurogenetics · 2026Review
- Gene-sized DNA insertion at genomic safe harbors in human cells using a site-directed transposase.Nucleic acids research · 2025Article
- Engineering of Zinc Finger Nucleases Through Structural Modeling Improves Genome Editing Efficiency in Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Nanoparticle-mediated delivery of non-viral gene editing technology to the brain.Progress in neurobiology · 2024Review
- OPA1 Dominant Optic Atrophy: Pathogenesis and Therapeutic Targets.Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society · 2023Article
- A universal deep-learning model for zinc finger design enables transcription factor reprogramming.Nature biotechnology · 2023Article
- A gene silencing screen uncovers diverse tools for targeted gene repression in Arabidopsis.Nature plants · 2023Article
- Live cell imaging of DNA and RNA with fluorescent signal amplification and background reduction techniques.Frontiers in cell and developmental biology · 2023Review
- Genome Editing and Diabetic Cardiomyopathy.Advances in experimental medicine and biology · 2023Article
- Stimuli-responsive nanoformulations for CRISPR-Cas9 genome editing.Journal of nanobiotechnology · 2022Review
- CRISPR-Cas-mediated transcriptional control and epi-mutagenesis.Plant physiology · 2022Review
- A deterministic code for transcription factor-DNA recognition through computation of binding interfaces.NAR genomics and bioinformatics · 2022Article
- Review
- Application of Engineered Zinc Finger Proteins Immobilized on Paramagnetic Beads for Multiplexed Detection of Pathogenic DNA.Journal of microbiology and biotechnology · 2021Article
- Titratable Pharmacological Regulation of CAR T Cells Using Zinc Finger-Based Transcription Factors.Cancers · 2021Article
- Tools for experimental and computational analyses of off-target editing by programmable nucleases.Nature protocols · 2021Review
- Epigenome engineering: new technologies for precision medicine.Nucleic acids research · 2020Article
- AMolecular and cellular biology · 2020Article
102 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
We have taken a comprehensive approach to the generation of novel DNA binding zinc finger domains of defined specificity. Herein we describe the generation and characterization of a family of zinc finger domains developed for the recognition of each of the 16 possible 3-bp DNA binding sites having the sequence 5'-GNN-3'. Phage display libraries of zinc finger proteins were created and selected under conditions that favor enrichment of sequence-specific proteins. Zinc finger domains recognizing a number of sequences required refinement by site-directed mutagenesis that was guided by both phage selection data and structural information. In many cases, residues not expected to make base-specific contacts had effects on specificity. A number of these domains demonstrate exquisite specificity and discriminate between sequences that differ by a single base with >100-fold loss in affinity. We conclude that the three helical positions -1, 3, and 6 of a zinc finger domain are insufficient to allow for the fine specificity of the DNA binding domain to be predicted. These domains are functionally modular and may be recombined with one another to create polydactyl proteins capable of binding 18-bp sequences with subnanomolar affinity. The family of zinc finger domains described here is sufficient for the construction of 17 million novel proteins that bind the 5'-(GNN)6-3' family of DNA sequences. These materials and methods should allow for the rapid construction of novel gene switches and provide the basis for a universal system for gene control.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.