June 10, 2024Nature Biomedical EngineeringOpen Access

Efficient site-specific integration of large genes in mammalian cells via continuously evolved recombinases and prime editing

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Authors

SPSmriti PandeyBroad Institute XGXin D. GaoBroad Institute NKN KrasnowBroad Institute

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Implication

Experimental evaluation demonstrates efficient integration of large genes in human cells using evolved recombinases and prime editing, highlighting new avenues for targeted gene therapy.

Key Points

Targeted integration of DNA cargoes exceeding 10 kilobases into human cell lines is markedly enhanced by coupling prime editing with phage-assisted continuous evolution of recombinases.
Integration efficiencies reached 60% for donor integration with engineered bxb1 recombinase variants, representing a 3.2-fold improvement over the wild-type enzyme.
Single-transfection experiments using passige achieved efficient insertion across primary human fibroblasts, supporting therapeutic gene writing in preclinical cell models.

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Pandey et al. (2024) studied this question.

synapsesocial.com/papers/68e65665b6db6435875e4e5b https://doi.org/10.1038/s41551-024-01227-1

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Implication

Experimental evaluation demonstrates efficient integration of large genes in human cells using evolved recombinases and prime editing, highlighting new avenues for targeted gene therapy.

Efficient site-specific integration of large genes in mammalian cells via continuously evolved recombinases and prime editing

Discussion

Member takes

Implication

Key Points

Cite This Study

Efficient site-specific integration of large genes in mammalian cells via continuously evolved recombinases and prime editing

Discussion

Member takes

Implication

Key Points

Cite This Study

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