Genome editing to model and reverse a prevalent mutation associated with MPN

[Manouche]

“Much work remains to be done regarding the safety of therapeutic gene editing, but there is accumulating evidence that causative mutations in monogenic hematopoietic disorders can be repaired in patient HSCs. Curing overtly oncogenic disorders using genome editing is difficult due to the need for complete allele conversion, since cells that escape the edit may eventually recover to take over the population. However, since the increased co-culture fitness of the JAK2 V617F mutation is a gradual event, it may be possible that even incomplete editing could lead to extended disease remission.”

journals.plos.org/plosone/a...

[MPort]

Thank you. These posts show scientific research that gives us hope.

[Aldebaran25]

Happy to see we are actively on the radar of CRISPR technology

[EmeraldA]

Thank you this has gave me some hope today!!

[hunter5582]

Very interesting. Perhaps someday a cure.

[Aneliv9]

Does this only apply to Jak2 mutation?

[Manouche in reply to Aneliv9]

This study only applies to Jak2, but regarding MPN genome editing potentially applies to all monogenic mutation.

[MPNBlog]

Hi ManoucheThanks for this link. Ever since I was diagnosed (Feb 2017 PV) I have wondered if a CRISPER cure was a possibility. My initial question was 'Why can't we just reverse the valine substitution for phenylalanine that causes the V617F mutation in the JAK2 gene? Surely CRISPER can do that?' When I asked, my original haem mused that that should be theoretically possible, but it wasn't as simple as that and there were a lot of complications with CRISPER, and it was very expensive. eg One problem that has arisen since then is unwanted deletions. The 'competitive growth advantage provided by the mutation' noted in the article seems a problem too unless every single mutated cell can be deleted. However, this article gives some hope that at least CRISPER is being considered. Surely a single mutation disease is a good place to start? I would think that any cure was a long way off however as these studies are still at the mouse level. I'm not aware of these researchers, but they are from UCSF. Hopefully this won't just disappear as some other initial research work has done. There just aren't enough MPNers to instigate significant research to really make a difference, such as the volume of research done in breast cancer for example.