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Cell ; 186(10): 2256-2272.e23, 2023 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-37119812

RESUMO

Applications of prime editing are often limited due to insufficient efficiencies, and it can require substantial time and resources to determine the most efficient pegRNAs and prime editors (PEs) to generate a desired edit under various experimental conditions. Here, we evaluated prime editing efficiencies for a total of 338,996 pairs of pegRNAs including 3,979 epegRNAs and target sequences in an error-free manner. These datasets enabled a systematic determination of factors affecting prime editing efficiencies. Then, we developed computational models, named DeepPrime and DeepPrime-FT, that can predict prime editing efficiencies for eight prime editing systems in seven cell types for all possible types of editing of up to 3 base pairs. We also extensively profiled the prime editing efficiencies at mismatched targets and developed a computational model predicting editing efficiencies at such targets. These computational models, together with our improved knowledge about prime editing efficiency determinants, will greatly facilitate prime editing applications.


Assuntos
Simulação por Computador , Edição de Genes , RNA Guia de Sistemas CRISPR-Cas , Sistemas CRISPR-Cas , Edição de Genes/métodos , Conhecimento , RNA Guia de Sistemas CRISPR-Cas/química , Especificidade de Órgãos , Conjuntos de Dados como Assunto
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