Breaking the Code using CRISPR: Novelty and Recent Breakthroughs

Ten years before CRISPR/Cas tool entered the picture with a bang, making the entire research community flabbergasted. Still, its presence is something to be bowed down for the immense solutions it brings along with it. The gene-editing tool CRISPR and its refinement according to the need is the big game. Some novel innovations in this field have been dealt with over here.

CRISPR plays a good role in synthetic biotechnology. The antique CRISPR/Cas9 had some flaws of off-target mutations and bounded use in large deletion knock-ins and knock-outs, making it unsuitable for bioprocessing applications. Cas-CLOVER, similar to CRISPR/Cas9, nullifies off-target possibilities and increases efficient knock-ins and knock-outs.

Fabricated Saccharomyces cerevisiae strains with female-directed RNAi using Cas-CLOVER can be used in mosquito infections treatment such as Encephalitis and West Nile. Interfering RNA pesticides (IRP) targeting female disease-causing mosquitoes cleave and silence genes needed for mosquito larvae’ existence. It is basically where the embellished yeast acts as potential larvicides.
CRISPR also lends a hand in tackling the energy crisis. Bacteria and algae function as powerhouses of biofuel production, but the challenges of meeting the commercial need are still a problem. Promisingly, CRISPR can solve the energy crisis in the world with a polish in the technology and companies that invest in the same.

CRISPR fine-tunes bacteria and algae to produce fuel in large amounts. Californian researchers with ExxonMobil and Synthetic Genomics have advanced this biofuel energy research. When algae stop getting food and sunlight, they move into the dormant stage, building up lipids. They have used CRISPR to knock out 18 of 20 transcription factors that regulate lipid production in algae. A recent announcement from the team stated that it will produce 10,000 barrels of algal biofuel per day by 2025.

Acetogenic bacteria capable of ethanol production are incapable of commercial exploitation using limited genetic tools. But in a recent study, CRISPR has involved remarkable gene deletion, making it a practicable tool for engineering this bacterium.

Nevertheless, to say, CRISPR’s aid in medicine is mind blogging. For several disease treatments, clinical trials are almost in their final stages.

A team of researchers from Spain working on muscular-congenital dystrophies offers hope of treating the disorders by CRISPR gene-silencing. Along with this, they are also checking for the base and prime editing techniques for correction.

CRISPR therapy prospect, nulabeglogene autogedtemcel (nula-cel) is a combination of patient’s hematopoietic stem cells and Cas9-sgRNA gene editing machinery that corrects the beta-globin gene and reinstates adult hemoglobin expression thereby curing sickle cell disease. Graphite Bio has dosed nula-cel in Phase ½ trial in its first patient.
CRISPR/Cas9 therapy has been developed that reduces kallikrein activity and prevents attacks in people living with hereditary angioedema (HAE). Recently the USFDA has given Intellia Therapeutics orphan drug designation for NTLA (potential candidate of CRISPR). It is now being studied in Phase1/2 trial with Type 1 and Type 2 HAE patients.
In vivo delivery methods of CRISPR prime editing tools and their improvements are being studied for the therapy of cardiovascular disease. In another interesting study, base editing strategy of CRISPR was used to mitigate oxidative injury in coronary artery disease.

COVID-19 is a blessing in disguise. The urge and expectation in the detection and treatment have increased the hype about gene editing technology.

In addition to the antigen test kit and PCRs, CRISPR technology has attracted researchers due to its simple yet specific setup in SARS-Cov2 detection. Studies on how a mutation in the different variants could introduce a mismatch to the previous primers and crRNAs in the CRISPR/Cas system will bring a breakthrough.
Studies on CRISPR-associated immunochromatographic technique of detection for SARS-Cov2 in which RT-PCR tested 153 COVID samples were checked using this technique and found to have 100% consistency proving to have specificity similar to conventional RT-PCR.

CRISPR’s function in the treatment of cancer has been progressive to date. Detection and monitoring of therapeutic monoclonal antibodies in the human serum is significant.

Detection of cancer therapeutic monoclonal antibody, called panitumumab, has been done with the help of CRISPR/Cas12a. It sensed the antibody at a 0.62pM detection limit along with selective discrimination with other monoclonal antibodies. This sensing platform not only opens the door for antibodies but also for other biomolecules.

The PI3K-AKT signaling pathways have been modified in tumor-infiltrating lymphocytes (TIL) from ovarian or cervical cancers by application of CRISPR knock-outs of AKT 1 and AKT 2. This setup amplified effector CD8+ cells and memory T cells when co-cultured with tumor cells, paving a possible treatment strategy in solid tumors.

Apart from medicine, the gene-editing tool CRISPR offers support to detect foreign microbes in food samples and foreign particles in the blood samples of humans.

CRISPR/Cas12a has been discovered for a fast and specific nucleic acid detection of an E.Coli strain that causes hemorrhagic colitis in beef samples and is a potential detection method for food-borne diseases.
Detection of cocaine in human plasma with CRISPR/Cas12a associated with magnetic nanoparticles is being studied to detect cocaine in human plasma. It has outstanding specificity and sensitivity with a detection limit of 33pM.

Gene editing technology, especially CRISPR, manipulates crops of the desired trait.

CRISPR knock-out of multiple copies of the gene responsible for the bitterness in Brassica juncea that has cabbage and mustard under its genus has been developed. The salad blend is soon to be available in the US markets.

Likewise, innovations in gene editing technology are piling up each day. By the time the above breakthroughs are studied, another set of CRISPR breakthroughs line up in the newsletter. Environmental issues, human disorders, undesired plant traits, etc. can be solved with the specific and customizable tool of gene editing, the CRISPR.

The Code of life can be changed- changed for the better. The breakthroughs and research in gene editing tell us that gene editing will soon be the solution for all of the problems happening over here and for the easy living of humans.