How CRISPR Can Help Cure Herpetic Stromal Keratitis

(Posted on Friday, February 9, 2024)

This story is part of a series on the current progression in Regenerative Medicine. This piece is part of a series dedicated to the eye and improvements in restoring vision. 

In 1999, I defined regenerative medicine as the collection of interventions that restore tissues and organs damaged by disease, injured by trauma, or worn by time to normal function. I include a full spectrum of chemical, gene, and protein-based medicines, cell-based therapies, and biomechanical interventions that achieve that goal.

The herpes simplex virus (HSV) is a highly prevalent virus that can cause various human infections. One of the most severe complications of HSV is herpetic stromal keratitis (HSK), which affects the cornea of the eye and can lead to visual impairment or even blindness. Unfortunately, current treatments for HSK are limited, and there is a pressing need for more effective therapies.

Fortunately, the gene-editing technology CRISPR-Cas9 has emerged as a promising approach for treating HSK caused by HSV. This revolutionary approach involves targeting and editing the viral genome to eliminate the virus from infected cells and tissues. The CRISPR-Cas9 system has shown great potential in laboratory studies, demonstrating high levels of efficacy against HSV.

Moreover, clinical trials are currently underway to evaluate the safety and efficacy of CRISPR-Cas9 for treating HSK caused by HSV. These trials have shown promising results, with some patients experiencing significant improvement in their vision and reduced corneal inflammation. The outcomes of these trials are being closely monitored, and researchers are hopeful that CRISPR-Cas9 will be a game-changer in treating HSK and other viral infections.

What is CRISPR?

CRISPR-Cas9 is a revolutionary tool in the world of gene editing. It is a targeted cutting and altering of the genetic code within organisms. This cutting-edge technology functions by using guide RNAs to target specific segments of DNA. Once the guide RNA is attached to the target gene, the Cas9 enzyme can cut the viral DNA in a precisely targeted manner.

This revolutionary technique boasts accuracy and efficiency. Once the Cas9 enzyme makes the intended cuts, researchers can add, remove, or repair genes to eliminate genetic disorders or fight viral infections.

The ability of CRISPR-Cas9 to selectively target and cut genes that are responsible for causing diseases such as herpes simplex virus (HSV) infections is what makes it a game changer in the field of biomedicine. It is also a versatile and controllable technique that can be modified to target various genetic mutations.

How Can It Be Used to Treat Herpes?

Several studies have demonstrated the effectiveness of CRISPR in treating HSV infections. For instance, a study on mice with herpetic stromal keratitis illustrated that targeting HSV-1 with CRISPR-Cas9 can cure the condition. The mice were treated with a single intravenous injection of CRISPR-Cas9 targeting the viral genome, significantly reducing viral replication and corneal pathology. 

Similarly, in another study, a single HSV-1-targeting CRISPR was injected into the cornea of three patients with severe refractory HSK during corneal transplantation. The treatment was safe and effective, with no detectable CRISPR-induced off-target cleavages or systemic adverse effects observed in all three patients for an average of 18 months. The patients showed significant improvement in symptoms, with no recurrence of HSV infections.

When studying human corneal epithelial cells, researchers discovered that using the CRISPR/Cas9 system to decrease NECTIN-1 can significantly lower the risk of HSV infection. Studies show that NECTIN-1 is a crucial receptor for HSV’s entry into cells. By reducing NECTIN-1 using the CRISPR/Cas9 system, viral replication and pathogenicity can be significantly decreased.

Assessing the Efficacy of CRISPR in Treating Herpes

Several studies have shown that CRISPR/Cas9 editing machinery could be used to control recurrent HSV ocular keratitis. The studies suggest that topical application of AAV-expressing CRISPR/Cas9 editing machinery can effectively prevent the spread of herpes simplex virus (HSV) in the eyes. Scientists use guide RNAs (gRNAs) to target specific genes in the virus and reduce the production of secreted virions that cause corneal pathology associated with HSV infections.

Recent clinical trials have shown promising results for using CRISPR-based therapies to treat herpes simplex virus (HSV). However, further research and development are still needed before these therapies become widely available. 

One of the significant concerns researchers are currently working on is addressing potential toxicity issues associated with using CRISPR. Obtaining FDA approval for human trials is also a crucial step in the process. While the potential benefits of CRISPR-based therapies for HSV are exciting, ensuring they are safe and effective before they can be made available to the public is essential.

Recent research has explored various delivery methods for CRISPR-based treatments for herpes. These treatments can be delivered through viral vectors, such as adeno-associated viruses, which can enter the host cells and have the CRISPR/Cas9 components. Local administration methods or lentiviral delivery can also target latent HSV-1-containing neurons. However, there are still concerns about these delivery methods’ long-term safety and efficacy in humans.

In conclusion, CRISPR-based therapies offer a promising avenue for improving the treatment of HSV infections and reducing the burden of associated diseases. However, more research and development are needed to address potential toxicity issues and optimize the delivery methods for CRISPR-based therapies. With continued efforts, CRISPR-based medicines can potentially revolutionize the treatment of HSV-caused corneal problems and other diseases caused by this virus.

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