Addressing the dNTP bottleneck restricting prime editing activity [preprint]

Authors
Ponnienselvan, Karthikeyan
Liu, Pengpeng
Nyalile, Thomas
Oikemus, Sarah
Joynt, Anya T
Kelly, Karen
Guo, Dongsheng
Chen, Zexiang
Lee, Jeong Min
Schiffer, Celia A
Student Authors
Thomas Nyalile
UMass Chan Affiliations
Biochemistry and Molecular Biotechnology
Li Weibo Institute for Rare Diseases Research
Molecular, Cell and Cancer Biology
Morningside Graduate School of Biomedical Sciences
Program in Molecular Medicine
RNA Therapeutics Institute
Wellstone Center for FSHD
Schiffer Lab
Document Type
Preprint
Publication Date
2023-10-29
Keywords
Biochemistry
prime editing efficiency
mutations

Metadata
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Link to Full Text
https://doi.org/10.1101/2023.10.21.563443
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.
Source
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.
DOI
10.1101/2023.10.21.563443
Permanent Link to this Item
http://hdl.handle.net/20.500.14038/52857
PubMed ID
37904991
Notes
This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.
Rights
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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