INTRODUCTION:

The finding of clustered regularly interspaced short palindromic repeats (CRISPR) and their role as an adaptive prokaryotic immune system together with genes associated with CRISPR paved the way for their adoption as a powerful genome engineering tool. Because of its specificity, efficacy, and simplicity, the CRISPR system is called the largest biotechnology discovery of the century, and it has opened up new possibilities for micro-genome editing and in vivo imaging. Overall, the CRISPR/Cas9 technology has shown the unprecedented clinical potential to study and target diseases and to provide new drug discovery techniques. It holds the promise, and perhaps most significantly, of new diagnostic and therapeutic interventions.

CRISPR has become the dominant methodology used in many studies of cancer biology due to the convenience of this technique. Scientists develop a revolutionary CRISPER based genome editing treatment to destroy cancer cells. This new development is a significant step on the way to finding a cure for cancer [1].

CRISPER/Cas9 is very effective in treating metastasis cancers. It is an innovative treatment for aggressive cancers that have no effective treatment today. It is not chemotherapy and it causes no side effects. Cancer cells treated using this method will never become active again. To examine the possibility of using the technology to treat cancer, scientists choose the deadliest cancers: glioblastoma and metastatic ovarian cancer [2].

Glioblastoma is the most aggressive type of brain cancer with a life expectancy of 15 months after diagnosis and a five-year survival rate of only 3%. Researchers demonstrated that a single treatment with CRISPER-LNPs doubled the average life expectancy of mice with gliobalstoma tumors. It also improved their overall survival rate by about 30%. For the study, the researchers develop a novel lipid nanoparticle-based delivery system that specifically targets cancer and destroys them by genetic manipulation. The system carries a messenger RNA which encodes for the CRISPER enzyme Cas9 that acts as molecular scissors and cuts the cell’s DNA. As a result, it neutralizes it and permanently prevents its replication [3,4].

The CRISPER genome editing technology, capable of identifying and altering any genetic segment has revolutionized the ability to disrupt, repair, or even replace genes. Clinical implementation is still in its infancy because an effective delivery system is needed to safely and accurately deliver the CRISPER to its target cells. Experiments are currently focusing on blood cancers that are very interesting genetically as well as genetic diseases such as Duchenne muscular dystrophy [5,6].

CRISPER guides:

The CRISPR tool consists of two key functions in the laboratory: a guide RNA and a DNA-cutting enzyme, most commonly called Cas9. The RNA guide is developed by researchers to mirror the DNA of the gene to be edited (called the target). Cas partners with the RNA guide and, true to its name, Cas contributes to the target. Cas cuts the DNA as the guidance RNA matches the DNA of the target gene. In certain circumstances, when it's restored, the target gene's DNA is scrambled and the gene is inactivated. Scientists may modify genes in more specific ways with other variants of CRISPR, such as inserting a new DNA section or modifying single letters of DNA [7].

To detect particular targets, such as DNA from cancer-causing viruses and RNA from cancer cells, researchers have also used CRISPR. CRISPR has most recently been used as an experimental test for the detection of the novel coronavirus [8,9].

Another plus is that it is easy to quickly scale up CRISPR. Hundreds of guide RNAs may be used by researchers to control and assess hundreds or thousands of genes at a time. This form of procedure is also used by cancer researchers to select out genes that may make ideal candidates for medications and as a bonus, Dr. Chavez noted that it's certainly cheaper than previous methods [10,11].

CRISPR is also entirely flexible. It can edit almost any DNA section within the 3 billion letters of the human genome, and it is more effective than other methods of editing DNA. With older approximations, Dr. Li said that creating a genetically modified mouse model normally takes a year, but within a few months, scientists can now create a complex mouse model with CRISPR [12].

Another plus is that CRISPR is easy to scale up fast. Researchers can use hundreds of guide RNAs to monitor and evaluate hundreds or thousands of genes at a time. Cancer researchers also use this type of technique to select genes that could be suitable candidates for drugs. Dr. Chavez noted, as an additional advantage, that it is cheaper than previous strategies [13].

CRISPR’s Limitations:

CRISPR isn't ideal, and many scientists have been skeptical about its use by humans because of its downsides. A big pitfall is that CRISPR often cuts DNA outside of the "off-target" editing of the target gene. As happened in a 2002 gene therapy study, scientists are concerned that such accidental changes could be dangerous and could even turn cells cancerous [14,15].

If CRISPR continues to split random pieces of the genome, in very odd ways, the cell will start stitching things together, and there is some fear about it being cancer. Bringing CRISPR components into cells is another possible roadblock. Co-opting a virus to do the job is the most common way to do this. The virus is modified to carry genes for the lead RNA and Cas instead of ferrying genes that cause disease.

One thing is to slip CRISPR into lab-grown cells, but it's another story to bring it into cells in the body of a human. Some viruses used to hold CRISPR can infect different cell types, so they can infect several cell types [16].

Studies on CRISPR treatment comes on the way:

Protection and viability of cell therapy dependent on CRISPR in humans Patients, but they have also developed extensive guidelines for Editing and monitoring CRISPR of non-target incidents in therapeutic environments which are helpful in the design of possible experiments. These, though are Studies have already shown some drawbacks to the modern editing of genes Technique. Next, gene editing efficiency varies greatly. Via patients and aim genes. This may be attributed to various protocols for cell development are used in different experiments, but The importance of maximizing and validating both of them is stressed. The second one, when discussing the non-target rates were moderate and large in all three trials. It is based on gRNA sorting and multiple editing of genes. The probability of chromosome transmission has significantly improved [17,18].

Twelve years ago, a study discussed mRNA treatments. People believed it was science fiction. It believes that many personalized treatments based on genetic messages for both cancer and hereditary diseases can be seen shortly by negotiating with international companies and institutions to realize the benefits for human patients of gene editing [19,20].

Although the NYCE T cell analysis marked the first trial of a cancer treatment dependent on CRISPR, more are expected to come. Other gene-editing methods will potentially build the next wave of therapies.

Other CRISPR research trials performed to cure cancer are also ongoing. CRISPR-engineered CAR T-cell therapies are being studied in a few trials and are another form of immunotherapy. For example, in individuals with B-cell cancers and people with multiple myeloma, one organization is researching CRISPR-engineered CAR T-cells [21,22].

There are also a lot of concerns on all the applications CRISPR could be used in the study and treatment of cancer. CRISPR tools are also being improved by humans. It's pretty active research and development area.

COCLUSIONS:

It will probably take some time before the new treatment can be used in humans. The whole scene of molecular drugs that use messenger RNA is growing. Most COVID-19 vaccines currently under development are based on this principle [23]. This technology opens numerous new possibilities for treating other types of cancer as well as rare genetic diseases and chronic viral diseases such as ADIS. Scientists hope to see personalized treatments based on genetic messengers for both cancer and genetic diseases. Future studies need to evaluate The Long-Ter-Up. It has been considered that CRISPR in the future will have much wider implementations.

ACKNOWLEDGMENTS:

The authors thank the College of Medicine, University of Mosul.

CONFLICT OF INTEREST:

The authors declare that there is no conflict of interest in this study.

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Received on 27.11.2020 Modified on 18.12.2020

Res. J. Pharma. Dosage Forms and Tech.2021; 13(1):54-56.

DOI: 10.5958/0975-4377.2021.00009.4