April 15, 2024
Treat herpetic stromal keratitis with CRISPR


This story is part of a series on current advances in regenerative medicine. This piece is part of a series dedicated to improving the eyes and restoring vision.

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

Herpes simplex virus (HSV) is a highly prevalent virus that can cause a variety of human infections. One of the most serious complications of HSV is herpetic stromal keratitis (HSK), which affects the cornea of ​​the eye and can cause visual impairment or even blindness. Unfortunately, current treatments for HSK are limited, and more effective treatments are urgently needed.

Fortunately, the gene-editing technology CRISPR-Cas9 has emerged as a promising approach to treat 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 a high level of efficacy against HSV.

Additionally, 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 improvements in vision and reduced corneal inflammation. The results of these trials are being closely monitored, and researchers hope that CRISPR-Cas9 will prove to be a game-changer in the treatment of HSK and other viral infections.

What is CRISPR?

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

This revolutionary technology boasts of accuracy and efficiency. Once the Cas9 enzyme makes the desired cut, 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 like herpes simplex virus (HSV) infection is what makes it a game changer in the field of biomedicine. It is also a versatile and controllable technology that can be modified to target different genetic mutations.

How can it be used to treat herpes?

Several studies have demonstrated the effectiveness of CRISPR in treating HSV infection. For example, a study in mice suffering from herpetic stromal keratitis showed that targeting HSV-1 with CRISPR-Cas9 could cure the condition. Mice treated with a single intravenous injection of CRISPR-Cas9 targeting the viral genome significantly reduced viral replication and corneal pathology.

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

When studying human corneal epithelial cells, researchers found that using the CRISPR/Cas9 system to knock down NECTIN-1 could significantly reduce the risk of HSV infection. Studies show that NECTIN-1 is an important receptor for HSV entry into cells. By reducing NECTIN-1 using the CRISPR/Cas9 system, viral replication and pathogenicity can be significantly reduced.

Assessing the efficacy of CRISPR in treating herpes

Several studies have shown that CRISPR/Cas9 editing machinery can be used to control recurrent HSV ocular keratitis. Studies show that topical application of AAV-expressing CRISPR/Cas9 editing machinery can effectively inhibit the spread of herpes simplex virus (HSV) in the eye. 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 infection.

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

One of the important concerns researchers are currently working on is addressing potential toxicity issues associated with the use of CRISPR. Getting FDA approval for human testing is also an important step in the process. While the potential benefits of CRISPR-based treatments for HSV are exciting, it is necessary to ensure that they are safe and effective before they are made available to the public.

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

In conclusion, CRISPR-based therapy offers a promising opportunity to improve the treatment of HSV infection and reduce the burden of associated diseases. However, more research and development is needed to address potential toxicity issues and optimize delivery methods for CRISPR-based therapies. With continued efforts, CRISPR-based drugs could potentially revolutionize the treatment of corneal problems caused by HSV and other diseases caused by this virus.

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