Illuminating the genome-wide activity of genome editors for safe and effective therapeutics
Open Access
- 22 December 2018
- journal article
- research article
- Published by Springer Science and Business Media LLC in Genome Biology
- Vol. 19 (1), 1-7
- https://doi.org/10.1186/s13059-018-1610-2
Abstract
Genome editing holds remarkable promise to transform human medicine as new therapies that can directly address the genetic causes of disease. However, concerns remain about possible undesired biological consequences of genome editors, particularly the introduction of unintended off-target' mutations. Here, we discuss both important considerations for therapeutic genome editing and our understanding of the functional impact of undesired off-target mutations. An important challenge for the future will be the development of new approaches for predicting and defining the probable function of unintended genome-editing mutations, which will inspire confidence in the next generation of promising genome-editing therapies.Funding Information
- St. Jude Children's Research Hospital (St. Jude Children’s Research Hospital Collaborative Research Consortium on Novel Gene Therapies for Sickle Cell Disease)
- Doris Duke Charitable Foundation (2017093)
- National Heart, Lung, and Blood Institute (U01HL145793)
This publication has 66 references indexed in Scilit:
- In silico abstraction of zinc finger nuclease cleavage profiles reveals an expanded landscape of off-target sitesNucleic Acids Research, 2013
- Nucleotide-resolution DNA double-strand break mapping by next-generation sequencingNature Methods, 2013
- Topological domains in mammalian genomes identified by analysis of chromatin interactionsNature, 2012
- Spatial partitioning of the regulatory landscape of the X-inactivation centreNature, 2012
- Repetitive DNA and next-generation sequencing: computational challenges and solutionsNature Reviews Genetics, 2011
- Histone H3K27ac separates active from poised enhancers and predicts developmental stateProceedings of the National Academy of Sciences of the United States of America, 2010
- Genome editing with engineered zinc finger nucleasesNature Reviews Genetics, 2010
- Histone modifications at human enhancers reflect global cell-type-specific gene expressionNature, 2009
- Quantification of random mutations in the mitochondrial genomeMethods, 2008
- Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genomeNature Genetics, 2007