Optimizing CRISPR-Cas technologies in Caenorhabditis elegans : Nested CRISPR and expanded targeting with Cas variants

In this thesis, I present an alternative, cloning-free method for the generation of endogenous fluorescent reporters in the nematode Caenorhabditis elegans. I demonstrate that Nested CRISPR is an efficient method that can be customized for the insertion of a suite of fluorescent tags and epitopes at...

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Detalles Bibliográficos
Autor: Vicencio, Jeremy
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/672604
Acceso en línea:http://hdl.handle.net/10803/672604
Access Level:acceso abierto
Palabra clave:Genome editing
CRISPR
Caenorhabditis elegnas
Genetic engineering
Cas9 variants
Edición genómica
Caernohabditis elegans
Ingeniería genética
Variantes de Cas9
575
Descripción
Sumario:In this thesis, I present an alternative, cloning-free method for the generation of endogenous fluorescent reporters in the nematode Caenorhabditis elegans. I demonstrate that Nested CRISPR is an efficient method that can be customized for the insertion of a suite of fluorescent tags and epitopes at endogenous loci using a combination of single-stranded and double-stranded DNA repair templates. In this thesis, I also demonstrate the use of enzymes other than Cas9 to target non-NGG PAM sites. The results show that AsCas12a can perform efficient genome editing in TTTV PAMs. Furthermore, the structurally engineered Cas9 variants SpG and SpRY can mediate genome editing in NGN and NYN PAMs, respectively, via both error-prone and precise repair mechanisms under optimized conditions.