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

RNA Editing02:23

RNA Editing

9.7K
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...
9.7K
Long-patch Base Excision Repair01:02

Long-patch Base Excision Repair

7.8K
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:
7.8K
What is Genetic Engineering?00:49

What is Genetic Engineering?

79.5K
Overview
79.5K
CRISPR/Cas9 Genome Editing01:28

CRISPR/Cas9 Genome Editing

1.6K
The CRISPR-Cas system serves as a bacterial defense mechanism against invading genetic elements such as viruses and plasmids, forming the foundation for its adaptation as a powerful genome-editing tool. Originally discovered in prokaryotes, this system has been repurposed to revolutionize genetic engineering across a wide range of organisms, including plants, animals, and humans. The core component, Cas9, is an endonuclease derived from Streptococcus pyogenes, capable of introducing...
1.6K
Base Excision Repair01:54

Base Excision Repair

25.9K
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...
25.9K
Conservative Site-specific Recombination and Phase Variation02:53

Conservative Site-specific Recombination and Phase Variation

6.6K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
6.6K

You might also read

Related Articles

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

Sort by
Same author

DNA Cut-Ligation Cyclization Surpasses Jacobson-Stockmayer J-Factor Expectations by over Threefold.

Biomolecules·2026
Same author

Probing the limits of genetic recoding using multi-omics-guided evolution.

Nature communications·2026
Same author

Derivation of elephant induced pluripotent stem cells.

Nature methods·2026
Same author

Programmable Nucleic Acid Sensing in Human Cells Using Circularizable ssDNA.

Nature communications·2026
Same author

What comes next? Follow through care after genetic diagnosis in infancy.

Pediatric research·2026
Same author

A Developmental Lectin-Glycan Program Enables Early Breast Cancer Dissemination and Metastatic Onset.

bioRxiv : the preprint server for biology·2026
Same journal

Spatially resolved profiling of extracellular vesicles in tissues with Spatial-EV-seq.

Nature biotechnology·2026
Same journal

Mapping the spatial landscape of extracellular vesicles in tissues with Spatial-EV-seq.

Nature biotechnology·2026
Same journal

Author Correction: Generation of modified cows and sheep from spermatid-like haploid embryonic stem cells.

Nature biotechnology·2026
Same journal

Toward mechanistic virtual immune cells.

Nature biotechnology·2026
Same journal

Mapping and engineering the human cell-cell interactome.

Nature biotechnology·2026
Same journal

Efficient generation of epitope-targeted antibodies with Germinal.

Nature biotechnology·2026
See all related articles
  1. Home
  3. Engineered Base Editors With Reduced Bystander Editing Through Directed Evolution.
  1. Home
  3. Engineered Base Editors With Reduced Bystander Editing Through Directed Evolution.

Related Experiment Video

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

1.6K

Engineered base editors with reduced bystander editing through directed evolution.

Ramiro M Perrotta1, Svenja Vinke2, Raphaël Ferreira2,3

  • 1Department of Genetics, Harvard Medical School, Boston, MA, USA. Ramiro_perrotta@hms.harvard.edu.

Nature Biotechnology
|December 18, 2025

View abstract on PubMed

Summary
This summary is machine-generated.

Researchers engineered adenine base editors (ABEs) for enhanced genome editing precision. This new method minimizes unwanted bystander edits, improving safety and efficiency for therapeutic applications.

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

5.9K
Enhanced Genome Editing with Cas9 Ribonucleoprotein in Diverse Cells and Organisms
09:51

Enhanced Genome Editing with Cas9 Ribonucleoprotein in Diverse Cells and Organisms

Published on: May 25, 2018

35.4K

Related Experiment Videos

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

1.6K
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

5.9K
Enhanced Genome Editing with Cas9 Ribonucleoprotein in Diverse Cells and Organisms
09:51

Enhanced Genome Editing with Cas9 Ribonucleoprotein in Diverse Cells and Organisms

Published on: May 25, 2018

35.4K

Area of Science:

  • Molecular Biology
  • Genetics
  • Biotechnology

Background:

  • Base editors offer precise genome modification but suffer from bystander edits, limiting their use.
  • Current precision strategies often reduce efficiency and are sequence-specific.

Purpose of the Study:

  • To develop an improved base editing system with minimized bystander edits and maintained high efficiency.
  • To establish a scalable framework for engineering highly precise base editors.

Main Methods:

  • Designed and tested 3'-extended guide RNAs for improved specificity.
  • Employed a precision-driven phage-assisted evolution system.
  • Utilized protein language models for enzyme variant evolution.

Main Results:

  • Identified context-dependent guide RNA variants that enhanced specificity.
  • Evolved adenine base editor variants 2-3x more precise than ABE8e.
  • Achieved high editing efficiency across diverse pathogenic contexts in vitro.

Conclusions:

  • Developed a parallel engineering approach optimizing guide RNAs and deaminase enzymes.
  • Created a scalable framework for base editor precision engineering.
  • Addressed a key challenge in genome editing, enhancing therapeutic potential.