{"doi":"10.1016/j.fertnstert.2023.02.040","title":"The history, use, and challenges of therapeutic somatic cell and germline gene editing","abstract":"The advent of directed gene-editing technologies now over 10 years ago ushered in a new era of precision medicine wherein specific disease-causing mutations can be corrected. In parallel with developing new gene-editing platforms, optimizing their efficiency and delivery has been remarkable. With their development, there has been interest in using gene-editing systems for correcting disease mutations in differentiated somatic cells ex vivo or in vivo or for germline gene editing in gametes or 1-cell embryos to potentially limit genetic diseases in the offspring and in future generations. This review details the development and history of the current gene-editing systems and the advantages and challenges in their use for somatic cell and germline gene editing. The advent of directed gene-editing technologies now over 10 years ago ushered in a new era of precision medicine wherein specific disease-causing mutations can be corrected. In parallel with developing new gene-editing platforms, optimizing their efficiency and delivery has been remarkable. With their development, there has been interest in using gene-editing systems for correcting disease mutations in differentiated somatic cells ex vivo or in vivo or for germline gene editing in gametes or 1-cell embryos to potentially limit genetic diseases in the offspring and in future generations. This review details the development and history of the current gene-editing systems and the advantages and challenges in their use for somatic cell and germline gene editing. The term clustered regularly interspaced short palindromic repeats, better known by its acronym CRISPR, is synonymous with gene editing. Clustered regularly interspaced short palindromic repeats first appeared in the National Center for Biotechnology Information PubMed database in 2002, where it was coined in a study describing a novel family of repetitive deoxyribonucleic acid (DNA) sequences interspaced by similarly sized nonrepetitive sequences that only exist in prokaryotes (1Jansen R. Embden J.D. Gaastra W. Schouls L.M. Identification of genes that are associated with DNA repeats in prokaryotes.Mol Microbiol. 2002; 43: 1565-1575Crossref PubMed Scopus (1322) Google Scholar). From 2002 through 2006, a total of 15 articles were published with the acronym CRISPR. In 2007, it was discovered that the array of repeats and nonrepetitive sequences represented a prokaryotic adaptive immune system designed to prevent productive host infection and lysis by bacteriophages (2Barrangou R. Fremaux C. Deveau H. Richards M. Boyaval P. Moineau S. et al.CRISPR provides acquired resistance against viruses in prokaryotes.Science. 2007; 315: 1709-1712Crossref PubMed Scopus (4123) Google Scholar). It was 5 years later when the power of a CRISPR-based system for use in gene editing was revealed. Jinek et al. (3Jinek M. Chylinski K. Fonfara I. Hauer M. Doudna J.A. Charpentier E. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.Science. 2012; 337: 816-821Crossref PubMed Scopus (10289) Google Scholar) published a landmark article in 2012 demonstrating that a CRISPR-associated nuclease (Cas9) bound to the ribonucleic acid (RNA) generated from repetitive sequences integrated into the bacterial genome became active and would cleave double-stranded DNA (dsDNA) sequences targeted by complementary RNA transcribed from the nonrepetitive CRISPR DNA sequences. More importantly, from a gene-editing perspective, this study demonstrated that the Cas9 endonuclease could be easily programmed with single RNA molecules known as guide RNAs (gRNA) to cleave any specific DNA target site. In the following year, these findings were extended whereby it was observed that including a single-stranded DNA (ssDNA) template possessing homology to the Cas9-gRNA target site could be used to introduce a DNA sequence of interest into cell lines and the genome of mice through a process known as homology-directed repair (HDR) (4Wang H. Yang H.","journal":"Fertility and Sterility","year":2023,"id":363615,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9481,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":493790,"name":"Eli Y. Adashi","orcid":"0000-0001-7730-1192","position":1,"is_corresponding":false},{"id":364428,"name":"Jon D. Hennebold","orcid":"0000-0002-6760-3733","position":2,"is_corresponding":false},{"id":710492,"name":"Junghyun Ryu","orcid":"0000-0001-8064-5762","position":0,"is_corresponding":true}],"reference_count":115,"raw_metadata":null,"created_at":"2026-07-19T01:14:32.510714Z","pmid":"36878350","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}