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
gene
• BUT
Ø There is mosaicism = embryos with different genetically
modified tissues
Ø Notable off-target effects (=mutations in other
unwanted places)
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
genetic modifications
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
symptoms
Ø new avenues for developing epigenetic therapies
against human diseases
14. The "Oviedo Convention" (1)
• Agreement from 1997
• A reference in the field of bioethics
• From the European council
Ø 34 out of 47 member countries have signed it
Ø Germany, Ireland, Malta and Monaco did not sign because
they refuse every manipulation of the human embryo (and)
abortion
Ø UK and Belgium neither, because they found it too restrictive
Ø 28 have ratified and applied it
• Not so easy to change
17. Some general ethical reflections
• The question of tolerance towards handicapped
persons
• Kant: the universal principle for ethics
Consider the other person as an "aim in
his/herself" and not as an instrument that I use,
that I manipulate
= as a mean (for my profit)
=> Consider other human beings as persons, having
rights, and not reducing them to an object, that
has no rights