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Long-patch Base Excision Repair01:02

Long-patch Base Excision Repair

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Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
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One of the common DNA damages is the chemical alteration of single bases by alkylation, oxidation, or deamination. The altered bases cause mispairing and strand breakage during replication. This type of damage causes minimal change to the DNA double helix structure and can be repaired by the base excision repair (BER) pathways. BER corrects damaged DNA sequences by removing the damaged base and restoring the original base sequence using the complementary strand as a template.
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Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
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Related Experiment Video

Updated: May 10, 2025

Efficient PAM-Less Base Editing for Zebrafish Modeling of Human Genetic Disease with zSpRY-ABE8e
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QBEmax is a sequence-permuted and internally protected base editor.

Jiacheng Hu1, Mengyue Guo1, Qiang Gao1

  • 1Qi Biodesign, Beijing, China.

Nature Biotechnology
|April 21, 2025
PubMed
Summary
This summary is machine-generated.

QBEmax, a novel cytosine base editor (CBE), achieves highly pure C-to-T edits with minimal unintended mutations. This stable editor shows promise for precise gene editing applications.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biotechnology

Background:

  • Cytosine base editors (CBEs) are valuable tools for gene editing.
  • Multiplex gene knockout applications are hindered by impure edits, indels, and off-target mutations.

Purpose of the Study:

  • To develop a highly efficient and precise base editor for gene editing.
  • To overcome limitations of existing CBEs in multiplex gene knockout.

Main Methods:

  • Development and characterization of a novel base editor, QBEmax.
  • Molecular dynamic modeling to assess editor stability and mechanism.
  • Evaluation of editing efficiency, product purity, indel formation, and off-target effects.

Main Results:

  • QBEmax demonstrates high editing efficiency with up to 99.8% C-to-T conversion.
  • The editor exhibits significantly reduced indel formation and off-target mutations.
  • Molecular modeling revealed QBEmax's compact and stable structure, protecting target bases.

Conclusions:

  • QBEmax represents a significant advancement in base editing technology.
  • Its high purity and low off-target activity make it suitable for precise gene editing.
  • QBEmax holds potential for improved multiplex gene knockout strategies.