How does gene editing work?

Описание: DNA editing, or gene editing, allows scientists to make precise edits in a specific DNA location. If a patient has a genetic disorder, such as Sickle Cell Disease, then a gene editing approach would produce a specific genetic modification in the DNA of red blood cells. This DNA edit would then allow red blood cells to produce healthy levels of hemoglobin protein. When done correctly, this should eliminate the disease symptoms associated with SCD.

In this video, I explain how gene editing works in the context of Sickle Cell Disease. We now have an FDA approved medicine based on CRISPR / cas9 DNA editing technology. CRISPR/cas9 is the most common gene editing technology. Casgevy was approved in December 2023, this was the first gene editing medicine to receive FDA approval in the US.

I explain the process of CRISPR in an ex vivo therapy and I describe the gene editing tools that make this therapy possible.

I explain how gene editing works in general. I also specifically describe the gene editing approach used by Vertex for their Casgevy drug.

In the video, I explore a few of these key points below.

1. Crispr/Cas9 can modify a specific genetic region on a specific chromosome. In contrast, gene therapy with AAV or lentivirus cannot do that.

2. For SCD, guide RNA is designed that will bind to a regulatory region of BCL11A. Once bound to this specific genetic region, the Cas9 enzyme will cut this DNA region and create a double strand break. BCL11A represses fetal hemoglobin. The intention is to disrupt this repressor (thereby increasing fetal hemoglobin).

3. For the SCD therapy, Guide RNA forms a pre-formed complex with Cas9 protein. This ribonucleoprotein complex is electroporated into bone marrow stem cells (after these cells are removed from the body). I didn't explain this step very clearly in the video.... I'll discuss this more in another video.

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

5. 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.

Sources:

Fyodur Urnov/The CRISPR Journal (BCL11A image)

https://www.genengnews.com/topics/gen...

https://www.genengnews.com/topics/gen...

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

These biotech videos are modified excerpts from professional courses I teach to clients in the life science industry. My clients include investors and employees at pharma, biotech, non-profit and government organizations. The intended audience is anyone with a basic understanding of biology (DNA, RNA, proteins, cells) that is also curious about the future of advanced medicine. I'll keep posting videos on this channel as long as they are useful. If you appreciate them.. like, comment, subscribe and share your thoughts. Thanks! *