A method for generating user-defined circular single-stranded DNA from plasmid DNA using Golden Gate intramolecular ligation.

Golden Gate assembly Intramolecular ligation ssDNA synthesis

Journal

Biotechnology and bioengineering
ISSN: 1097-0290
Titre abrégé: Biotechnol Bioeng
Pays: United States
ID NLM: 7502021

Informations de publication

Date de publication:
10 2023
Historique:
revised: 26 05 2023
received: 02 12 2022
accepted: 05 06 2023
pmc-release: 01 10 2024
medline: 15 9 2023
pubmed: 27 6 2023
entrez: 27 6 2023
Statut: ppublish

Résumé

Construction of user-defined long circular single stranded DNA (cssDNA) and linear single stranded DNA (lssDNA) is important for various biotechnological applications. Many current methods for synthesis of these ssDNA molecules do not scale to multikilobase constructs. Here we present a robust methodology for generating user-defined cssDNA employing Golden Gate assembly, a nickase, and exonuclease degradation. Our technique is demonstrated for three plasmids with insert sizes ranging from 2.1 to 3.4 kb, requires no specialized equipment, and can be accomplished in 5 h with a yield of 33%-43% of the theoretical. To produce lssDNA, we evaluated different CRISPR-Cas9 cleavage conditions and reported a 52 ± 8% cleavage efficiency of cssDNA. Thus, our current method does not compete with existing protocols for lssDNA generation. Nevertheless, our protocol can make long, user-defined cssDNA readily available to biotechnology researchers.

Identifiants

pubmed: 37366288
doi: 10.1002/bit.28471
pmc: PMC10527171
mid: NIHMS1908527
doi:

Substances chimiques

DNA, Single-Stranded 0
DNA 9007-49-2

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

3057-3066

Subventions

Organisme : NIGMS NIH HHS
ID : R21 GM129559
Pays : United States

Informations de copyright

© 2023 Wiley Periodicals LLC.

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Auteurs

Isabell K Strawn (IK)

Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado, USA.

Paul J Steiner (PJ)

Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado, USA.

Matilda S Newton (MS)

Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado, USA.

Zachary T Baumer (ZT)

Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado, USA.

Timothy A Whitehead (TA)

Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado, USA.

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Classifications MeSH