CRISPR gene editing has made rapid progress heading from bench to bedside. Perhaps the fastest has been its progress toward clinical use to combat sickle cell disease. We’ll start with a new paper on one major effort here.
CRISPR gene editing. This process often involves cutting DNA, which then can be used as an opening to make specific changes to the sequence.
CRISPR sickle cell
CRISPR-Cas9 Editing of the HBG1 and HBG2 Promoters to Treat Sickle Cell Disease, NEJM. There are several approaches to using gene editing for sickle cell disease, including inhibiting BCL11A to boost fetal hemoglobin. This paper reports on a Novartis Phase 1/2 sickle cell trial. The data are encouraging. They conclude: “CRISPR-Cas9 disruption of the HBG1 and HBG2 gene promoters was an effective strategy for induction of fetal hemoglobin. Infusion of autologous OTQ923 into three participants with severe sickle cell disease resulted in sustained induction of red-cell fetal hemoglobin and clinical improvement in disease severity.”
More regenerative reads
- Perfect Pitch: Genome Editing Pioneer Fyodor Urnov on Commercializing CRISPR Therapies and Epigenomic Tuning, Genedge. This is a nice video chat with the wonderful Fyodor Urnov about CRISPR translation and clinical applications.
- Generation of a humanized mesonephros in pigs from induced pluripotent stem cells via embryo complementation, Cell Stem Cell. This is an interesting but still fairly limited study. They got a good percentage of human cells in primordial kidney tissue in the pigs. However, to do that they expressed one of my favorite genes, MYCN, which is a powerful oncogene. It’s hard to imagine that hIPSCs with exogenous MYCN are entirely normal and have it in the mix could certainly could convey a higher risk of cancer in any organ recipient. With the addition of BCL2 for these hIPSCs, you are already a couple of steps toward cancer more generally too. Another concern here is that they saw some human cells in the pig brains too, raising potential ethical challenges. Maybe these things can be addressed moving forward.
- Emily Mullin wrote about the new paper on human pig chimeras over at Wired too and quoted me. I wrote about human chimeras for Wired in 2016. Many of the same core issues remain.
- Apical size and deltaA expression predict adult neural stem cell decisions along lineage progression, Sci. Adv.
- Symmetric inheritance of parental histones governs epigenome maintenance and embryonic stem cell identity, Nat. Gen.
- Stem cell scientist and bit.bio founder launches new startup with goal of extending healthspan by 20 years, Endpoints. Here’s another group trying to defy aging and death. I haven’t seen anything yet though in the same orbit as Altos Labs.
- Aspen to collect patient data remotely before its cell therapy trial, Parkinson’s News Today. I just wrote recently about another Parkinson’s Disease effort by BlueRock Therapeutics, whose early trial based on ES cell-derived dopaminergic neurons looked encouraging.
Stem cells used to successfully treat arthritis in gorilla at Budapest zoo, Univ. of Sheffield.