He then discussed the prerequisites for success when applying genetic editing which are as follows:
- A tractable disorder
- A causative gene
- A target tissue
- An editing tool
CRISPR – Cas9 is an editing tool and refers to ‘Clustered Regularly Interspersed Short Palindromic Repeats’ and Cas9 is the enzyme. This forms part of the bacterial adaptive immune system. The Cas9 enzyme plus the guide/protein RNA complex ensures that the viral DNA is cut at the right place. The cell survives by disabling the virus. By using this tool there is the potential to modify any gene within the genome using guide RNA directed at human sequences of DNA.
The type of edits are as follows, with example diseases that will potentially benefit from the therapies shown in brackets:
- Knockouts – inactivation /deletion of the gene-causing sequence
(TTR (transthyretin-type systemic) amyloidosis, hypercholesterolaemia)
- Repairs – correction of the ‘misspelled’ disease-driving DNA sequence
(haemachromatosis, alpha 1 antitrypsin deficiency)
- Inserts – insert new DNA sequence to produce a therapeutic protein
(haemophilia A and B)
CRISPR is the therapy to fix the broken gene in genetic diseases.
The promise of a potential cure for haemophilia B reminded me of my days as a paediatric registrar seeing a young boy repeatedly attending the ward for infusions of factor 9. I recall his distress at the repeated venepunctures not to mention the impact on his schooling and family life. How fantastic if we could cure this serious disease and others like it.
Following his talk there were some short presentations from four panellists (Dr Matthew Garnett, Dr Sarah Chan, Dr Alison Kay and Dr Nicola McCarthy) followed by a roundtable session. During this session the need to engage the public was mentioned despite this being difficult as the science is challenging to communicate. Nicola talked about the advantage of being able to screen cancer drugs by using primary cells rather than established lines. Alison (lay representative) mentioned that important issues to consider for CRISPR were understanding, accessibility, timescale and accountability. Finally, Sarah talked about the ethical aspects asking us to consider what is an acceptable risk and emphasising that we need to carefully consider the off-target effects. There was also some further discussion about the ethics of germline gene editing and the need to consider the socio-cultural context.
I found the lecture and subsequent discussion extremely informative and thought provoking. The promise of a potential cure for haemophilia B reminded me of my days as a paediatric registrar seeing a young boy repeatedly attending the ward for infusions of factor 9. I recall his distress at the repeated venepunctures not to mention the impact on his schooling and family life. How fantastic if we could cure this serious disease and others like it.
The 2019 FORUM Annual Lecture can be viewed in its entirety at https://youtu.be/r0bUu3rJ9Ks
Header image credit: Ernesto del Aguila III, National Human Genome Research Institute, NIH
Portrait image credit: Abi Moore