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Related Concept Videos

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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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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Bacteria and archaea are susceptible to viral infections just like eukaryotes; therefore, they have developed a unique adaptive immune system to protect themselves. Clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas) are present in more than 45% of known bacteria and 90% of known archaea.
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The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
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Generation of Defined Genomic Modifications Using CRISPR-CAS9 in Human Pluripotent Stem Cells
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CRISPR/Cas gene editing in the human germline.

B Bekaert1, A Boel1, G Cosemans1

  • 1Ghent-Fertility And Stem cell Team (G-FaST), Department for Reproductive Medicine, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, Belgium.

Seminars in Cell & Developmental Biology
|March 20, 2022
PubMed
Summary

Human germline gene editing (HGGE) offers potential for correcting mutations but faces challenges like mosaicism. Research is exploring stem cells to predict HGGE outcomes before clinical use.

Keywords:
Base editingCRISPR/Cas9Human germline gene editingLoss-of-heterozygosityMosaicismPrime editing

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Area of Science:

  • Genetics
  • Developmental Biology
  • Biotechnology

Background:

  • CRISPR/Cas9 technology enables permanent genetic modifications in embryos.
  • Human germline gene editing (HGGE) holds promise for correcting inherited diseases.
  • Significant hurdles, including mosaicism and loss-of-heterozygosity, impede clinical application.

Purpose of the Study:

  • To review the current state of human germline gene editing in oocytes and embryos.
  • To highlight the challenges and limitations of HGGE.
  • To discuss the utility of alternative models, such as stem cells, for predicting HGGE outcomes.

Main Methods:

  • Review of existing literature on CRISPR/Cas9-mediated HGGE.
  • Analysis of experimental parameters affecting HGGE success.
  • Evaluation of stem cell models for assessing genetic outcomes.

Main Results:

  • HGGE success is contingent on numerous experimental factors.
  • Mosaicism and loss-of-heterozygosity are critical challenges.
  • Stem cell models show potential for predicting HGGE efficacy.

Conclusions:

  • HGGE is a rapidly advancing field with therapeutic potential.
  • Overcoming technical and ethical challenges is crucial for clinical translation.
  • Further research using alternative models is needed to ensure safety and efficacy.