CRISPR: Does it help diseased plants and humans alike?

Last Updated on February 9, 2023 by Joseph Gut – thasso

February 07, 2023 – CRISPR is a genetic engineering technique by which the genomes of living organisms may be modified. It is based on a simplified version of the bacterial CRISPR–Cas9 antiviral defense system. By delivering the Cas9 nuclease complexed with a synthetic guide RNA  (gRNA) into a cell, the cell’s genome can be cut at a desired location, allowing existing genes to be removed and/or new ones added in vivo.

The technique is considered highly significant in biotechnology and medicine as it enables editing genomes in vivo very precisely, cheaply, and easily. It can be used in the creation of new medicines, agricultural products, and genetically modified organisms, or as a means of controlling pathogens and pests infestations without interventions by widespread chemicals. It also has possibilities in the treatment of inherited genetic diseases as well as diseases arising from somatic mutations such as cancer.

When it comes to CRISPR-based treatment, or better yet, prevention, in a plant disease, then the efforts related to Pierce’s disease would be a point in case. Pierce’s disease, caused by the bacterium Xylella fastidiosa, is one of the most significant threats to grapevines and its growing industries. This bacterium lives in the xylem (water conducting system) of the grapevines plants. It uses several vectors, among them most promimently the glassy-winged sharpshooter for spreading; in fact, less than a decade after it was first identified in California, an invasive glassy-winged sharpshooter had turned the bacterium that causes Pierce’s from a nuisance to a nightmare in grapevine plantages.

By classical means such as through inspections and targeted pesticide spraying, California has largely been able to confine the invasive sharpshooter to Southern California. But the disease still has no cure, and it’s at risk of getting worse and harder to combat due to climate change. This is why researchers are now looking to add cutting-edge CRISPR technology to California’s anti-Pierce’s arsenal, by targeted changing the genome of the glassy-winged sharpshooter so that it can no longer spread the bacterium.

While from the scientific point of view this may not be too great a challenge it may be from the regulatory and approval side of things however. In the US, the Environmental Protection Agency (EPA) notes that the regulatory environment around CRISPR-modified insects is currently “evolving. Thus, government guidance released in 2017 outlined a coordinated approach that suggested that the U.S. Department of Agriculture (USDA) shall largely have authority over genetically engineered animals related to agriculture. But jurisdiction may vary depending on whether an edited organism is intended to reduce the population of an insect or disrupt disease transmission. Thus far, the US government has allowed the release of genetically modified mosquitoes, but tests of crop pests, like diamondback moths and pink bollworms, have been limited. It will be interesting to follow the progress of approval by authorities of the release into the environment of genetically manipulated glassy-winged sharpshooter and their contribution on the eventual eradication of Pierce’s disease.

In humans, CRISPR gene editing has been in development for quite some time now in attempting to treat complicated clinical conditions or prevent the development of rare diseases in individuals altogether. There are no FDA-approved CRISPR-based therapies yet. However, in 2023, several companies are expected push forward the development of CRISPR-based therapies through clinical trials or even obtaining FDA approval. Thus, Editas Medicine is aiming for a clinical update from the Phase I/II RUBY trial, which tests the CRISPR-Cas12a therapy EDIT-301 in SCD in mid-2023. Intellia plans to file an IND for NTLA-3001, a CRISPR-mediated

therapy for alpha-1 antitrypsin deficiency, sometime this year. The company also plans to start a Phase II study for NTLA-2002, a CRISPR therapy for hereditary angioedema in 2023. Additionally, Graphite Bio expects proof-of-concept data from a Phase I/II study in mid-2023 for its SCD treatment nula-cel. Nula-cel is part of the UltraHDR platform, which the company describes as the next generation of gene editing. In contrast, and a bit more advanced, Vertex and CRISPR Therapeutics have announced already in 2022 global regulatory submissions for Exa-cel, a CRISPR-based gene therapeutic approach for Sickle Cell Disease and Beta Thalassemia, when Exa-cel was granted Fast Track, Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug designations in the U.S., and Priority Medicines (PRIME) and Orphan Drug designations in Europe.

CRISPR gene editing also aims to treat heart disease and repair damaged tissue after a heart attack. In a study  recently published in the Science Journal, researchers  describe a cardioprotective strategy potentially applicable to a broad range of patients with heart disease. They used base editing to ablate the oxidative activation sites of CaMKIIδ, a primary driver of cardiac disease and showed in cardiomyocytes derived from human induced pluripotent stem cells that editing the CaMKIIδ gene to eliminate oxidation-sensitive methionine residues confers protection from ischemia/reperfusion (IR) injury. Moreover, CaMKIIδ editing in mice at the time of IR enables the heart to recover function from otherwise severe damage. CaMKIIδ gene editing may thus represent a permanent and advanced strategy for heart disease therapy.

Overall, CRISPR-based therapies seems carry an enormous potential for disease treatment and prevention in organisms so far apart like insects/plants and humans.This is just plain fascinating.

See here a short sequence on gene editing, CRISPR-technics included:

Disclaimer: The images and/or videos (if any) on this blog may be protected by copyright. All rights remain with the owner of these rights.