Addressing the dNTP bottleneck restricting prime editing activity [preprint]
Ponnienselvan, Karthikeyan Liu, Pengpeng Nyalile, Thomas Oikemus, Sarah Joynt, Anya T Kelly, Karen Guo, Dongsheng Chen, Zexiang Lee, Jeong Min Schiffer, Celia A
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Abstract
Prime editing efficiency is modest in cells that are quiescent or slowly proliferating where intracellular dNTP levels are tightly regulated. MMLV-reverse transcriptase - the prime editor polymerase subunit - requires high intracellular dNTPs levels for efficient polymerization. We report that prime editing efficiency in primary cells and in vivo is increased by mutations that enhance the enzymatic properties of MMLV-reverse transcriptase and can be further complemented by targeting SAMHD1 for degradation.
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Ponnienselvan K, Liu P, Nyalile T, Oikemus S, Joynt AT, Kelly K, Guo D, Chen Z, Lee JM, Schiffer CA, Emerson CP, Lawson ND, Watts JK, Sontheimer EJ, Luban J, Wolfe SA. Addressing the dNTP bottleneck restricting prime editing activity. bioRxiv [Preprint]. 2023 Oct 29:2023.10.21.563443. doi: 10.1101/2023.10.21.563443. PMID: 37904991; PMCID: PMC10614944.
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This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.