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Related Concept Videos

CRISPR01:59

CRISPR

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Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced...
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RNA Editing02:23

RNA Editing

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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...
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Genome Copying Errors02:46

Genome Copying Errors

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DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their  survival. Therefore, the copying errors are checked and repaired at three levels.
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Conservative Site-specific Recombination and Phase Variation02:53

Conservative Site-specific Recombination and Phase Variation

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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...
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Point and Frameshift Mutations01:30

Point and Frameshift Mutations

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Point mutations are genetic alterations involving the change of a single nucleotide base pair in DNA. Depending on how the alteration affects protein synthesis, they can lead to various consequences.Point mutations fall into the following types:Silent mutations occur when a nucleotide change does not alter the amino acid sequence due to the redundancy of the genetic code. For instance, changing ACC to ACA still encodes threonine, leaving the protein function unaffected. This occurs because...
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CRISPR/Cas9 Genome Editing01:28

CRISPR/Cas9 Genome Editing

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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...
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Adenine Base Editing Potently Suppresses Hepatitis B Surface Antigen Expression and Inhibits Hepatitis D Virus Release.

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Multiplex gene-editing strategy to engineer allogeneic EGFR-targeting CAR T-cells with improved efficacy against solid tumors.

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Platform solutions for commercial challenges to expanding patient access and making gene editing sustainable.

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Base editing HbS to HbG-Makassar improves hemoglobin function supporting its use in sickle cell disease.

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High-efficiency base editing in the retina in primates and human tissues.

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Updated: Nov 8, 2025

Efficient PAM-Less Base Editing for Zebrafish Modeling of Human Genetic Disease with zSpRY-ABE8e
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Rationally Designed Base Editors for Precise Editing of the Sickle Cell Disease Mutation.

S Haihua Chu1, Michael Packer1, Holly Rees1

  • 1Beam Therapeutics, Cambridge, MA, USA.

The CRISPR Journal
|April 20, 2021
PubMed
Summary
This summary is machine-generated.

New inlaid base editors (IBEs) expand gene editing capabilities by enabling precise DNA modifications at new locations. These engineered editors show higher efficiency and reduced off-target effects, offering therapeutic potential for genetic diseases like sickle cell anemia.

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Enhanced Genome Editing with Cas9 Ribonucleoprotein in Diverse Cells and Organisms
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Area of Science:

  • Molecular Biology
  • Gene Editing Technologies
  • Biochemistry

Background:

  • Base editors enable programmable DNA base conversions without double-strand breaks.
  • Targeting limitations exist due to the requirement for specific Cas9 protospacer adjacent motifs.

Purpose of the Study:

  • To engineer novel base editors with expanded targeting range and improved efficiency.
  • To overcome limitations of existing base editors by repositioning deaminase domains.

Main Methods:

  • Structure-guided design of inlaid base editors (IBEs) by integrating deaminase domains within Cas9.
  • Assessment of editing windows, efficiency, and off-target effects (DNA and RNA) of IBEs.
  • Application of IBEs for correcting the sickle cell hemoglobin allele in patient-derived hematopoietic stem cells.

Main Results:

  • Several IBE variants demonstrated shifted editing windows and enhanced editing efficiency.
  • IBEs enabled editing of targets previously inaccessible with standard base editors.
  • Reduced DNA and RNA off-target editing frequencies were observed with IBEs.
  • Successful conversion of the pathogenic sickle cell allele to the HbG-Makassar variant in patient cells.

Conclusions:

  • Inlaid base editors represent a significant advancement in gene editing, broadening targeting scope and improving precision.
  • IBEs offer a promising therapeutic strategy for genetic disorders, exemplified by the potential correction of sickle cell anemia.