ArticleNucleic acids research2009
Enhanced gene repair mediated by methyl-CpG-modified single-stranded oligonucleotides.
Article in Nucleic acids research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Modification of improved-genome editing via oviductal nucleic acids delivery (i-GONAD)-mediated knock-in in rats.BMC biotechnology · 2021Article
- High Homology-Directed Repair Using Mitosis Phase and Nucleus Localizing Signal.International journal of molecular sciences · 2020Article
- Urine mRNA to identify a novel pseudoexon causing dystrophinopathy.Annals of clinical and translational neurology · 2019Article
- A Standard Methodology to Examine On-site Mutagenicity As a Function of Point Mutation Repair Catalyzed by CRISPR/Cas9 and SsODN in Human Cells.Journal of visualized experiments : JoVE · 2017Article
- To cleave or not to cleave: therapeutic gene editing with and without programmable nucleases.Nature reviews. Drug discovery · 2017Article
- Genetic spell-checking: gene editing using single-stranded DNA oligonucleotides.Plant biotechnology journal · 2016Review
- Regulation of Gene Editing Activity Directed by Single-Stranded Oligonucleotides and CRISPR/Cas9 Systems.PloS one · 2015Article
- Emerging gene editing strategies for Duchenne muscular dystrophy targeting stem cells.Frontiers in physiology · 2014Review
- A high-content, high-throughput siRNA screen identifies cyclin D2 as a potent regulator of muscle progenitor cell fusion and a target to enhance muscle regeneration.Human molecular genetics · 2013Article
- Genome-wide methylation profiles reveal quantitative views of human aging rates.Molecular cell · 2013Article
- Oligonucleotide delivery by nucleofection does not rescue the reduced proliferation phenotype of gene-edited cells.Nucleic acid therapeutics · 2012Article
- DNA damage response pathway and replication fork stress during oligonucleotide directed gene editing.Molecular therapy. Nucleic acids · 2012Article
- Progress and prospects: oligonucleotide-directed gene modification in mouse embryonic stem cells: a route to therapeutic application.Gene therapy · 2011Review
- An update on targeted gene repair in mammalian cells: methods and mechanisms.Journal of biomedical science · 2011Review
- Subtle gene modification in mouse ES cells: evidence for incorporation of unmodified oligonucleotides without induction of DNA damage.Nucleic acids research · 2010Article
- Review
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene editing mediated by oligonucleotides has been shown to induce stable single base alterations in genomic DNA in both prokaryotic and eukaryotic organisms. However, the low frequencies of gene repair have limited its applicability for both basic manipulation of genomic sequences and for the development of therapeutic approaches for genetic disorders. Here, we show that single-stranded oligodeoxynucleotides (ssODNs) containing a methyl-CpG modification and capable of binding to the methyl-CpG binding domain protein 4 (MBD4) are able to induce >10-fold higher levels of gene correction than ssODNs lacking the specific modification. Correction was stably inherited through cell division and was confirmed at the protein, transcript and genomic levels. Downregulation of MBD4 expression using RNAi prevented the enhancement of gene correction efficacy obtained using the methyl-CpG-modified ssODN, demonstrating the specificity of the repair mechanism being recruited. Our data demonstrate that efficient manipulation of genomic targets can be achieved and controlled by the type of ssODN used and by modulation of the repair mechanism involved in the correction process. This new generation of ssODNs represents an important technological advance that is likely to have an impact on multiple applications, especially for gene therapy where permanent correction of the genetic defect has clear advantages over viral and other nonviral approaches currently being tested.
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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.