1 / 9

CRISPR/Cas9 and Germline Genome Editing for Muscular Dystrophy Treatment in Mice

This study explores the use of CRISPR/Cas9 technology to correct genetic defects in the Dmd gene responsible for Duchenne Muscular Dystrophy (DMD) in mice. Researchers developed mdx mouse models and utilized CRISPR/Cas9 to edit germline DNA. The results showed varying levels of mosaicism but no significant negative effects on treated mice. While the potential for muscle repair is promising, ethical considerations regarding human germline editing remain contentious. The study emphasizes the need for specific safety criteria before clinical applications can be considered.

hogue
Télécharger la présentation

CRISPR/Cas9 and Germline Genome Editing for Muscular Dystrophy Treatment in Mice

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. CRISPR Cas9 Genome Editing in Germlines PBIO 4500 December 5, 2017 Sarah Disney

  2. What is CRISPR Cas9? • Discovered in E. coli • CRISPR = Clustered Regularly Interspaced Short Palindromic Repeats • An adaptive bacterial immune defense • Cas9 = An endonuclease that uses a sgRNA to cleave a piece of DNA • NHEJ = Non-homologous end joining • HDR = homology directed repair

  3. Prevention of muscular dystrophy in mice by CRISPR/Cas9–mediated editing of germline DNA • Bassel-Duby et. Al • The objective of this study was to correct the genetic defect in the Dmd gene of mice with muscular dystrophy through CRISPR/Cas9 mediated germline editing • Did it work???

  4. Duchenne Muscular Dystrophy (DMD) • X-linked disease • 1 in 3,500 live male births • Rare in girls • Extremely debilitating • Muscle weakness and degeneration • Eventually fatal • Begins to affect heart and respiratory muscles

  5. Methodology • Developed DMD mice models • Referred to as mdx • Crossed mdx female and male to create mdx zygotes • CRISPR/Cas9 was used to treat the germlines in vitro • Zygotes were then reimplanted in a healthy mother • This lead to mice with varying levels of mocaisism • Referred to as mdx-C mice

  6. Results • Varying levels of mosaicism were effective • Direct editing of satellite cells in vivo by the CRISPR/Cas9 system represents a potentially promising alternative approach to promote muscle repair in DMD. • No significant negative effects were found in the treated mice

  7. Ethics • The ethics of human germline experimentation may be the most contentious conversation in science • At the NAS Summit 2015, the NAS ruled that “it would be irresponsible to proceed with any clinical use of germline editing”. • Specific safety and ethical criteria must be met before any use • Additionally, the baby would have to be at imminent risk of severe genetic disease with no other viable options • At what point is the use of a human embryo no longer justified? • Where do we draw the line? • Are we playing God?

  8. References • Long, C., McAnally, J. R., Shelton, J. M., Mireault, A. A., Bassel-Duby, R., & Olson, E. (2014). Prevention of muscular dystrophy in mice by CRISPR/Cas9–mediated editing of germline DNA. Science, 345(6201), 1184-1188. doi:10.1126/science.1254445 • Sharma, A., & Scott, C. (2015). The ethics of publishing human germline research. Nature Biotechnology, 33(6).

More Related