Gene Editing Inside the Body Using CRISPR

Summary

This video discusses a significant advancement in gene editing using CRISPR-Cas9, focusing on the first in vivo trial called BRILLIANCE. It highlights how CRISPR technology, which utilizes a combination of the Cas9 enzyme and guide RNA, is being applied to treat Leber congenital amaurosis type 10 through sub-retinal injections. By targeting a specific mutation in the CEP290 gene, researchers hope to restore gene function and improve vision. While the primary focus is on safety, the trial represents a crucial step toward realizing the potential of CRISPR-Cas9 in treating inherited diseases directly within the body.

Takeaways

• 🧬 CRISPR-Cas9 is a groundbreaking gene editing tool derived from bacterial defense mechanisms, known for its cost-effectiveness and precision.
• 🔬 The BRILLIANCE trial represents a significant advancement, as it is the first in vivo clinical trial utilizing CRISPR technology directly within the human body.
• 💉 Traditional gene editing treatments have relied on ex vivo methods, which involve removing cells from the body, modifying them, and reinfusing them.
• 👁️ The trial focuses on treating Leber congenital amaurosis type 10, a genetic disorder that leads to severe vision loss.
• 🛠️ The gene editing process uses a combination of the Cas9 enzyme and guide RNA to accurately target and modify specific DNA sequences.
• 🔄 The guide RNA contains a 20 base pair sequence designed to match the target DNA, allowing for precise cutting of the genetic material.
• ⚠️ The trial primarily focuses on the safety of the treatment, with efficacy being monitored as results become available.
• 🧫 The delivery system for the CRISPR components is an adeno-associated virus, which transports the gene-editing machinery directly to the affected cells.
• 🔍 Researchers aim to correct a specific mutation in the CEP290 gene that disrupts normal gene function, potentially restoring sight to affected individuals.
• 📈 This trial marks a crucial step in moving CRISPR technology from laboratory experiments to real-world medical applications, with hope for treating various genetic diseases.

Q & A

What is CRISPR-Cas9 and why is it significant in gene editing?

CRISPR-Cas9 is a gene editing tool adapted from bacterial defense mechanisms. It is significant because it is cheap, precise, and highly adaptable, allowing researchers to edit genes in living organisms.

What is the difference between ex vivo and in vivo gene editing?

Ex vivo gene editing involves taking cells out of the body, editing them, and then infusing them back in. In vivo gene editing, on the other hand, involves editing genes directly within the body without removing cells.

What condition is the BRILLIANCE trial targeting?

The BRILLIANCE trial is targeting Leber congenital amaurosis type 10, a genetic disorder that affects photoreceptor cells in the retina, leading to severe early-onset vision loss.

How does the CRISPR-Cas9 mechanism work at a molecular level?

CRISPR-Cas9 works by using a Cas9 enzyme to cut DNA at specific locations guided by a unique RNA sequence. If the RNA matches the DNA, Cas9 cleaves the double helix, which can knock out a gene or allow for gene repair.

What is the role of the adeno-associated virus vector in the gene editing process?

The adeno-associated virus vector acts as a delivery system that carries the Cas9 protein and guide RNAs to target cells in the body for gene editing.

What mutation in the CEP290 gene is the trial aiming to correct?

The trial aims to correct an intronic mutation in the CEP290 gene that leads to the inclusion of a cryptic exon, causing the gene to malfunction and resulting in vision loss.

What surgical procedure is involved in administering the gene editing drug?

The drug is administered through a sub-retinal injection, which requires surgery to make incisions in the eye and remove the vitreous gel for precise placement of the injection under the retina.

What are researchers looking to evaluate in the BRILLIANCE trial?

Researchers in the BRILLIANCE trial are primarily focused on assessing the safety of the gene editing drug, while also monitoring its efficacy in restoring vision.

What challenges exist in the application of CRISPR-Cas9 technology?

There is considerable uncertainty surrounding the long-term safety and effectiveness of CRISPR-Cas9 technology, as it is still being developed and tested in real-world applications.

How many patients are being enrolled in the BRILLIANCE trial?

The BRILLIANCE trial is looking to enroll 18 patients to test the gene editing treatment.