Can DNA Editing (CRISPR Technology) Treat Genetic Disease?

The discovery of deoxyribonucleic acid (DNA) as the genetic material and coding of information within it has been the driving principle used in biomedical research activities all over the world. Scientists are currently exploiting the microbiological techniques including polymerase chain reactions (PCR) and DNA cleavage by the restriction enzymes in executing molecular research practical (1). The exploitation of knowledge about DNA and the products it codes for, together with high throughput scientific techniques has made it possible to modify the genotypic and phenotypic traits of organisms through genome editing. Genes are targeted using technologies resulting in their alterations at specific segments or locus on the chromosome in the cells to be modified (6). The possibility of editing DNA is an approach perceived as instrumental for treating genetic disorders and associated disease. Thus, this article discusses the impact of technology on society concerning DNA editing technology (CRISPR) use in the treatment of genetic disorders.

Genome Editing

Editing of the genetic material is termed as the modification of DNA by the use of technologies thereby allowing scientists to change the originally encoded gene product. The process of genome editing entails adding, removing, or replacing a given gene with the intended one to produce the traits desired in the organism. The alteration of genetic materials has produced what the community of scientists call “genetically modified organisms (GMOs)” (6). However, the exploitation of the same principles on human beings has been limited following the associated costs and safety concerns demanded by ethics in scientific research.

The common techniques utilized for DNA editing include Zinc-Finger Nucleases (ZFNs) which exhibit cutting and binding domains of the DNA separately. The two domains of ZFNs can be initiated to form a double strand that can be easily manipulated. Transcription Activator-Like Effector Nucleases (TALENs) are also employed in DNA editing, and exhibit the same mechanism as the ZNFs but differ from the origin of operations (5). The two techniques employ the use of restriction enzymes but target different sites for cleaving the DNA. Also, ribonucleic acid-guided engineered nucleases (RGENs) which are commercially produced form part of the gene-editing tools in bioscience research. The principles of RGENs application generates mutations in a controlled manner that allow for mutations induction, hence gene alteration achieved (6). The technologies have been instrumental in achieving gene editing in fulfilling the objectives of biomedical research. However, their applicability to treating genetic complications in human beings is unsafe and unreliable, save for the recently developed CRSPIR-Cas9 technology.

The CRISPR Technology

The genetic disorders and diseases in human beings, however, require a reliable and risk-free technology to employ in treating them. The development of CRISPR-Cas9 system produced an efficient, cost-friendly, and very precise in DNA modification as compared to the initially available techniques. The principle exploited in CRISPR-Cas9 was obtained from the mechanism of bacterial protection against phage DNA (5). By allowing for DNA cleavage at a predetermined position, the technology has been validated for human genome editing. Basically, CRISPR-Cas9 uses the DNA cleaver (Cas9, which a nuclease) that is directed to the site or position of cutting by an RNA strand. The directing RNA strand binds to the gene segment targeted, thereby attaching the Cas9 to cleave the DNA (1). Mutations can then be induced at the cleaved section by deletion or insertion. Having benefit cutting across multiple sectors of the economy, with more impacts realized in agriculture, it implies that genome editing is for the wellbeing and good health of human beings.

Genome editing by CRISPR technology has principal use in the treatment of human beings gene associated with diseases and animal DNA modifications for high productivity. With the central focus on animal laboratory and cell culturing, therapeutic approaches are designed and remedies are generated by CRISPR-Cas9 system to cure cancer, haemophilia, and cystic fibrosis which endanger human life highly (10). Many clinical trials are run in biomedical laboratory facilities all over the world, especially in the developed nations, to develop immunotherapies using cell lines to cure leukaemia and pancreatic carcinomas. It implies that the application of CRISPR technology can be instrumental in lowering the fatality or risk factors of illnesses which are genetically associated, whether inheritable or developed from the lifestyle lived. For instance, diabetes, cardiovascular disorders, and neuropathies are linked to genetics, however, the environment and lifestyle also influence them (10). Reducing the intensity with which the mentioned health conditions impact the society has a possibility through the exploitation of CRISPR-Cas9 system.

The advancements CRISPR-Cas93 system have been viable mostly on the non-human primates where transcriptomics are initiatively used to develop epigenetic effects to pilot clinical studies. Through multiple studies and clinical trials, the technology has been successful in mitigating Duchenne Muscular Dystrophy (DMD) and genetically transmissible type I tyrosinemia. However, for the purposes of safety and long-term application due to its reliability, CRISPR-Cas93 should be evaluated across all dimensions of its use as a technical tool for treatment or mitigating genetic disorders. The capacity of existing CRISPR strategies in attenuating life-threatening syndromes which are hereditary is high and delivers promising results (4). On the contrary, the side effects left by the genetic deformations are not all alleviated in the process of treatment, leaving patients in psychological or social trauma.

Clinical Trials of CRISPR Technology in Human Medicine

The application of CRISPR-Cas9 technology is under trials for reliability in mitigating human genetic disorders and diseases, irrespective of the type of complication challenging patients’ lives. With the central focus on its safety for use, the technology has been invested in type 1 programmed cell death (PD1) knockout and treating complications arising from Epstein-Barr virus (EBV) infections at advanced stages. The case of EBV mitigation process entails the engineering of T-lymphocytes to suppress malignancies developed. Moreover, the principled involved is applicable in managing carcinomas that develop in the urinary bladder, pancreas, prostate, and the oesophagus.

Scientists have been extracting T cells from the patients attacked by the gene associated diseases, and utilizing the CRISPR-Cas9 to induce mutations by cutting out or silencing targeted genes. Thereafter, they infuse the same patients from which the cells were obtained with in vitro modified T lymphocytes after prior treatment with hydrocortisone or cyclophosphamide. The analysis involves monitoring the adverse effects of the use of CRISPR gene editing and medicines applicable in the process (10). It acts as an indication that the efficiency of utilizing the technology in managing genetic disorders is reliable. Besides, peripheral blood phlebotomy was executed to evaluate the immunotherapeutic aspect of altering the genome of T-lymphocytes. By monitoring the level of cytokines like interferons and tumour necrosis factors, together with oncogenes circulating in the peripheral blood, it is conceivable that the technology produces positive results (4). The practicality of CRISPR-Cas9 technology in mitigating diseases and relieving their adverse effects implies that it is valuable for treating genetic disorders.

Reflective Commentary

Genes are the principle machinery upon which all existing lives depend on. It through the genetic coding within the DNA that various proteins are generated to support the living systems at the cellular level. Unfortunately, genetic alterations occur through various processes of mutation leading to unintended proteins, which eventually merge as a complication to the whole human, animal, or plant physiological functions (8). Manipulation of the genes has been approached by multiple techniques, including selective breeding, to avoid the impact of disorders linked to the DNA constituents of an organism. Owing to technological advancements, editing of the genetic material has been made possible through biotechnology and genetic engineering. The CRISPR-Cas9 technology is one of the instruments through which alterations of human DNA can be achieved. It is termed as a refined technique following its efficiency and safety, together with economic reliability when employed to produce results (3). Among the field in which it is applied is medicine, cutting across biomedical research to clinical application in treating genetic disorders or diseases associated with the human DNA.

The CRISPR-Cas9 technology has been asserted as an avenue to alleviate health conditions linked to the human genome and diseases which stem intracellularly from the DNA mutations. The practicality of using the technology relies on the lifesaving capacity it exhibits together with the affordability of the services entailed in its application. Moreover, it is associated with minimal chances of succumbing to the operations as well as incurring deformations or pain (6). For instance, the CRISPR-Cas9 is employed in regenerative medicine to remedy genetically linked type 1 diabetes in the United States. The research is driven towards replacing the pancreatic cells producing insulin hormone in patients with diabetes mellitus. By carrying out ex-vivo engineering of cells derived from patients and infusing them back, transplant rejection risks are eliminated. Moreover, the stress for accessing compatible donors who consent for surgical operations is diminished, together with the costs incurred for a successful treatment to be executed (4). Following the promising effects of CRISPR-Cas9 technology in mitigating type 1 diabetes as per the feasibility tests through biomedical research, it is believed that insipidus (type II diabetes) can also be remedied by using it. It implies that CRISPR-Cas9 technology is vital for treating cellular deformations which turns out as health complications in human beings.

Sickle cell anaemia is one of the major problems in human health all over the world. The acquisition of sickle cell disease is through sex-linked genes transferred from the parents to their offspring. It implies that the disease is carried forward from one generation to another via chromosomal genes encoding for the production of the erythrocytes (7). In the United States, the Food and Drug Administration (FDA) permitted experimental research for the use of CRISPR-Cas9 technology in treating sickle cell anaemia. The procedure to be employed an encompassed modification of stem cells obtained from the patients. Thereafter, the successfully altered cells are to be infused back to a substantial quantity of haemoglobin to facilitate maximum oxygen transport. The sickle-shaped red blood cells have the insufficient quantity, and to some extent zero amount of haemoglobin to help in the transport of oxygen to body tissues (2). By genetically modifying the haematopoietic stem cells which generate erythrocytes in patients which sickle cell trait, a lifetime treatment can be achieved. Hence, CRISPR-Cas9 technology is vital for curbing genetically associated disorders like sickle cell anaemia.

The CRISPR-Cas9 technology has also been found viable for making alterations in the human or animal genomes, which can be inherited by offspring from the parents. The target of modifying within the genetic materials is the embryos which are either viable or not viable in the case of human health research. For instance, in 2015, scientists from China employed CRISPR-Cas9 technology in attempting to reconstitute the human embryo DNA to produce desirable traits. The motive of the researchers was to correct the potentially dangerous defect called beta-thalassemia by modifying the genes encoding for it (9). Even though success through CRISPR-Cas9 in mitigating the complication wasn’t promising, it opened for further innovative research involving gene-editing techniques to develop a working treatment.

Research on the embryonic stem cell editing using CRISPR-Cas9 has delivered promising results in mitigating hypertrophic cardiomyopathy. The complication is developed by young athletes and possesses a high rate of fatality. Modification of embryos by researchers from Oregon Health and Science University yielded the best results ever desired by athletes and even produced a relevant genetic constitution. With a feasibility rating at 72.4%, from the research, it validated that inheritable traits can be transferred to all generations by editing the genome of parents (6). The CRISPR-Cas9 technology, therefore, has in store the potential benefits when utilized in correcting genetic disorders.

Conclusion

Gene editing entails alteration of the DNA sequences of an organism to produce the desired traits. It stands as an instrument through which health disorders and diseases that are genetically linked can be treated. By removing the undesired genes and replacing them with the ones encoding desirable traits, genetic disorders become treatable. The CRISPR-Cas9 technology stands are preferable following its safety and economic factors associated with it. With existing feasible experiments results, it is conceivable that gene-editing technology is instrumental for mitigating human genetic complications.

Reference List

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