[svsaraf]

You are out of date. CRISPR is extremely effective in live patients, usually packaged in a virus or lipid nano particle.

While CRISPR is often used in cultured cells (eg for CAR T therapies) there are CRISPR therapeutics in live human patients today in phase 3 trials for sickle cell disease (among other indications).

[est31]

The phase 3 trials you mention were probably for exa-cel, a therapy that involves removing the cells from the patient, editing them with CRISPR in the dish. Meanwhile you do myeloablation of the patient, aka destroy their bone marrow, then put in the repaired cells. The key here is: the application of CRISPR happens outside of the patient.

https://doi.org/10.1056/nejmoa2031054

> Approximately 80% of the alleles at this locus were modified, with no evidence of off-target editing. After undergoing myeloablation, two patients - one with TDT and the other with SCD - received autologous CD34+ cells edited with CRISPR-Cas9 targeting the same BCL11A enhancer.

Similar (not the same) things have already been done multiple times for HIV patients who had to have their bone marrow destroyed for other reasons, generally leukemia (Düsseldorf Patient, Geneva Patient, London Patient, etc). They received transplants from donors that had mutations in CCR5, which prevents HIV. But you can't cure 40 million people living with HIV that way.

This therapy is extremely involved, expensive, and it also impacts the health of the patient (e.g. their entire immune memory is reset, they have to redo all their vaccinations). You don't destroy the bone marrow of someone due to no reason. Them requiring regular blood transfusions is a good reason, but them having to take antiretroviral drugs once per day is generally not seen as one.

The paper of this thread is about a single injection that does these CRISPR edits while inside the patient, without involving destruction of the bone marrow.