How does the new gene editing drug work?

I present a short video describing how Casgevy works for Sickle Cell Disease

Hello friends,

In December 2023, the FDA approved the first gene editing drug in the U.S.

Casgevy is now commercially available for adults and adolescents that have recurrent pain crises from Sickle Cell Disease.

I spend much of my time traveling around the country and teaching educational seminars at life science conferences. In the past year, I’ve come to appreciate that most people who work in the life science industry don’t really understand how this gene editing drug works.

In the 8 minute video below, I explain how gene editing works in general. I also specifically describe the gene editing approach used by Vertex for their Casgevy drug.

You need to appreciate a few key points:

1. Gene editing (i.e. Crisper/Cas9) can modify a specific genetic region on a specific chromosome. In contrast, gene therapy with AAV or lentivirus cannot do that.

2. Crispr/Cas9 does not appear to be efficient at inserting corrected repair template (HDR), it’s better at inserting mutations (indels via NHEJ)

3. For the Sickle Cell drug, you need to understand the difference between fetal hemoglobin and adult hemoglobin… and how the Casgevy drug tweaks with the timing of fetal hemoglobin expression in order to compensate for a mutated version of adult hemoglobin.

I touch on these topics in video below.

Kevin