This is a brief introduction to the CRISPR/Cas9 genome editing technique and a quick review of two articles that have to do with potential applications in humans. There is a draft for an ethical reflexion.
7. What is CRISPR-Cas9?
The copied sequence from the virus is used to guide the CRISPR-Cas9 complex to
the complementary viral DNA and to cut it!
Clustered Regularly Interspaced Short Palindromic Repeats
Bacterial Defense Mechanism
11. Tests in China (3) : results
• They manage to "reach", to cleave, the ß-globin
Ø There is mosaicism = embryos with different genetically
Ø Notable off-target effects (=mutations in other
Ø Embryo cells also use other endogenous homologous
genes/sequences to repair the targeted gene (7 cases)
Ø In 4 cases, embryos with the targeted mutation (based
on designed injected ssDNA)
• Still far away from a secure clinical application !
13. Use of CRISPR/Cas9 for clinical
purposes without gene editing (2)
• Salk Institute (California), Izpisua-Belmonte's lab
• Idea: activate the target genes without creating
Ø recruitment of Cas9 and transcriptional activation
complexes by guide RNAs
Ø proof-of-concept: treatment of mouse-models of
diabetes, molecular dystrophy and acute kidney disease
Ø measurable phenotypes and amelioration of disease
Ø new avenues for developing epigenetic therapies
against human diseases