Progress for Gene Therapy and CRISPR against Blood Diseases

[Ygggdrasil]

The New England Journal of Medicine published two papers showing data for successful treatment of a handful of patients with sickle cell disease or β- thalassemia using gene therapy techniques. Both teams used the strategy of inhibiting the BCL11a transcription factor in blood cells, which allows the cells to express fetal hemoglobin that can compensate for the loss of the "adult" hemoglobin that is defective in these diseases. One team used the strategy of inserting a shRNA into the blood cells to post-transcriptionally repress the BCL11a gene while the other team inactivated the BCL11a gene using CRISPR. The treatments, however, are quite risky and expensive as they involve extracting bone marrow from the patients, changing the DNA of those cells in the lab, then performing a full bone marrow transplantation with the re-engineered cells.

Here's a link to the two papers:
Post-Transcriptional Genetic Silencing of BCL11A to Treat Sickle Cell Disease
https://www.nejm.org/doi/full/10.1056/NEJMoa2029392

CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia
https://www.nejm.org/doi/full/10.1056/NEJMoa2031054

Popular press coverage:
https://www.sciencemag.org/news/202...chnologies-wont-lead-designer-babies/']crispr-and-another-genetic-strategy-fix-cell-defects-two-common-blood-disorders[/URL]
https://blogs.sciencemag.org/pipeline/archives/2020/12/07/gene-therapy-absolutely-and-for-realA different gene therapy strategy was published a few years ago showed similarly successful results against sickle cell disease:
https://www.physicsforums.com/threa...in-one-patient-for-at-least-15-months.906352/

 

[BWV]

Another of the CRISPR IP triumvirate, Intellia Therapeutics is paired with Novartis to attack sickle cell, curious what the difference is between this and the CRISPR Therapeutics / Vertex collaboration above:

This Phase 1/2 clinical trial will begin investigating OTQ923 in adult patients with severe complications of SCD. OTQ923 is a SCD treatment based on genome editing of hematopoietic stem cells (HSCs), using CRISPR/Cas9 RNA guides identified through Intellia’s cell therapy research collaboration with Novartis. This therapeutic approach results in highly targeted editing of the HSC’s DNA to induce fetal hemoglobin (HbF) expression. The edited cells are returned to the patient, where the expression of HbF is expected to reduce the deleterious effects of sickle hemoglobin (HbS). Novartis’ IND application triggered a milestone payment to Intellia, and the company is eligible to receive additional downstream success-based milestones and royalties.

https://ir.intelliatx.com/news-rele...chnologies-wont-lead-designer-babies/']crisprcas9[/URL]

 

[Ygggdrasil]

Another of the CRISPR IP triumvirate, Intellia Therapeutics is paired with Novartis to attack sickle cell, curious what the difference is between this and the CRISPR Therapeutics / Vertex collaboration above

Sounds like they're using a very similar strategy, though there's not enough scientific details in the press release to judge. Vertex/CRISPR Therapeutics seems to have a big head start, however. According to ClinicalTrials.gov, the Vertex/CRISPR Therapeutics trials began back in 2018 while the Novartis/Intellia trial just started in June 2020.