Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Base Excision Repair01:54

Base Excision Repair

22.3K
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.
The first step of...
22.3K
RNA Editing02:23

RNA Editing

9.0K
RNA editing is a post-transcriptional modification where a precursor mRNA (pre-mRNA) nucleotide sequence is changed by base insertion, deletion, or modification. The extent of RNA editing varies from a few hundred bases, in mitochondrial DNA of trypanosomes, to a just single base, in nuclear genes of mammals. Even a single base change in the pre-mRNA can convert a codon for one amino acid into the codon for another amino acid or a stop codon. This type of re-coding can significantly affect the...
9.0K
Long-patch Base Excision Repair01:02

Long-patch Base Excision Repair

7.0K
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:
7.0K
Proofreading01:31

Proofreading

6.3K
Synthesis of new DNA molecules is carried out by the enzyme DNA polymerase, which adds nucleotides on the daughter strand complementary to the template DNA strand. DNA polymerase has a higher affinity to add the correct base and ensures fidelity during DNA replication. Furthermore,  it exhibits proofreading activity during replication, using an exonuclease domain that cuts off incorrect nucleotides from the nascent DNA strand.
Errors During Replication are Corrected by the DNA Polymerase...
6.3K
Mismatch Repair01:20

Mismatch Repair

4.8K
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.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
4.8K
Improving Translational Accuracy02:07

Improving Translational Accuracy

10.3K
Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
10.3K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Author Correction: Increasing the efficiency and targeting range of cytidine base editors through fusion of a single-stranded DNA-binding protein domain.

Nature cell biology·2026
Same author

Redirection of SARS-CoV-2 to phagocytes by intranasal sACE2-Fc as a universal decoy confers complete prophylactic protection.

eLife·2026
Same author

Maternal obesity induces macrophage to myofibroblast transition in kidneys of male offspring through a pathway driven by 20-hydroxyeicosatetraenoic acid.

Nature communications·2026
Same author

Discovery and Characterization of Benzamide Derivatives as Highly Potent SUCNR1 Antagonists for Cancer Immunotherapy.

Journal of medicinal chemistry·2026
Same author

Chidamide synergizes with cisplatin-etoposide to trigger pyroptosis and anti-tumor immunity in diffuse large B-cell lymphoma.

Communications medicine·2026
Same author

Structural insights into measles virus RNA synthesis regulation and pan-paramyxoviral polymerase inhibition by ERDRP-0519.

Proceedings of the National Academy of Sciences of the United States of America·2026

Related Experiment Video

Updated: Jun 29, 2025

Efficient PAM-Less Base Editing for Zebrafish Modeling of Human Genetic Disease with zSpRY-ABE8e
07:31

Efficient PAM-Less Base Editing for Zebrafish Modeling of Human Genetic Disease with zSpRY-ABE8e

Published on: February 17, 2023

1.1K

Engineering APOBEC3A deaminase for highly accurate and efficient base editing.

Lei Yang1, Yanan Huo1, Man Wang1

  • 1Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.

Nature Chemical Biology
|March 30, 2024
PubMed
Summary

Engineered cytosine base editors (CBEs) achieve highly accurate C-to-T conversions with minimal off-target effects. These precise genome editing tools show promise for treating genetic diseases.

More Related Videos

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors
09:22

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Published on: February 28, 2021

5.5K
A Nonsequencing Approach for the Rapid Detection of RNA Editing
08:50

A Nonsequencing Approach for the Rapid Detection of RNA Editing

Published on: April 21, 2022

2.6K

Related Experiment Videos

Last Updated: Jun 29, 2025

Efficient PAM-Less Base Editing for Zebrafish Modeling of Human Genetic Disease with zSpRY-ABE8e
07:31

Efficient PAM-Less Base Editing for Zebrafish Modeling of Human Genetic Disease with zSpRY-ABE8e

Published on: February 17, 2023

1.1K
Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors
09:22

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Published on: February 28, 2021

5.5K
A Nonsequencing Approach for the Rapid Detection of RNA Editing
08:50

A Nonsequencing Approach for the Rapid Detection of RNA Editing

Published on: April 21, 2022

2.6K

Area of Science:

  • Molecular Biology
  • Genome Editing
  • Biochemistry

Background:

  • Cytosine base editors (CBEs) enable C-to-T conversions but face limitations due to off-target and bystander effects.
  • Existing CBEs exhibit variable efficacy influenced by DNA methylation and sequence context.

Purpose of the Study:

  • To engineer highly accurate and efficient adenine base editors (haA3A-CBEs) with reduced off-target activity.
  • To assess the therapeutic potential of haA3A-CBEs in a mouse model of tyrosinemia.

Main Methods:

  • Structure-guided engineering of human APOBEC3A (A3A) deaminase to create novel haA3A-CBE variants.
  • Compatibility testing with PAM-relaxed SpCas9-NG for precise targeting of pathogenic mutations.
  • In vivo delivery using adeno-associated virus (AAV) and lipid nanoparticle (LNP)-based mRNA in a mouse model.

Main Results:

  • Developed haA3A-CBE variants with a narrow editing window and near-background off-target DNA and RNA activity.
  • Achieved up to 58.1% editing efficiency in mouse liver tissue for tyrosinemia, with minimal bystander editing.
  • LNP-based mRNA delivery further reduced off-target effects compared to AAV delivery.

Conclusions:

  • Engineered haA3A-CBEs offer enhanced precision and efficiency for C-to-T base editing.
  • These advanced CBEs demonstrate significant potential for developing novel therapies for genetic diseases.
  • The developed system overcomes limitations of previous base editors, paving the way for clinical applications.