Abstract
Introduction
Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) is a technique developed by mimicking nature. 1 Cas9 (CRISPR-associated protein 9) is an enzyme. The Cas9 enzyme uses the CRISPR sequence as a guide for DNA cleavage and opens up the DNA strands at specific places. 2 CRISPR-Cas9 technology is enabling scientists to edit the genes within living organisms, leading to a great revolution in scientific research and further application advancements and healthcare management of rare diseases.3, 4 CRISPR & Cas9 is an important tool for treating diseases by the process of gene editing and permanently correcting deleterious base mutations. It involves the disruption of disease-causing genes with great precision and efficiency. 5
The CRISPR technology has progressed from a prokaryotic immune defense to a basic technology in genome engineering and precision medicine. 5 In 1987, it was initially identified in Escherichia coli in the form of unexplained repetitive DNA elements. Afterwards, with further development and research, its role in the adaptive immune mechanism of archaea and bacteria was studied.6, 7 It works with the use of Cas9 enzymes in combination with the CRISPR sequence. It used to cut DNA precisely at specific locations. This enables removal, addition and alteration of genetic material, causing a huge impact. 8
This revolutionary technology has wide applications in basic biological research, biotechnological product development and has great potential in treating many rare diseases.7, 8 The mutation-specific interventions in monogenic disorders such as sickle cell anemia, Beta-thalassemia and Leber congenital amaurosis are being enabled with the successful use of CRISPR/Cas9 technology. 9 In spite of such important intervention and application of CRISPR technology-based therapies, its global implementation has not happened at speed due to infrastructural disparities, deficient standard regulatory framework and increasing ethical concerns. 10
The medicolegal aspects of CRISPR technology include a wide range of ethical and legal considerations which are crucial for its development, application and further progress.
CRISPR Technologies Application in the Healthcare Industry
CRISPR/Cas9 is used as genetic scissors to cut, edit or insert the DNA at a specific place precisely. It has a great application in medicine.
Medical applications related to the treatment of disease: Over 300 million individuals are suffering from rare diseases worldwide, and most of these conditions are of monogenic origin. These are the diseases with early onset, limited treatment plans and high morbidity. Monogenic disorders such as sickle cell anemia, Beta-thalassemia and Leber congenital amaurosis are being treated with the successful use of CRISPR/Cas9 technology.
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There is a global disparity between the diagnosis and access to care. The equitable patient’s access is hindered by infrastructural, regulatory and systemic barriers. Medical applications related to Forensic Medicine
Forensic DNA: CRISPR-based rapid DNA tests will be helpful to identify pathogens or individuals from a crime scene sample rapidly and precisely. Antimicrobial use: CRISPR is used to target the antibiotic-resistant bacteria, which may be helpful in death investigations. Gene therapy: CRISPR is helpful in the treatment of rare genetic disorders like thalassemia, sickle cell disease and certain cancers. Such clinical trials are allowed in India.
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Forensic medicine angle:
Identification: If DNA is edited, there may be issues related to DNA fingerprinting and confirmation of identity.
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Cause of death: In deaths while performing CRISPR trials, postmortem examination needs to be conducted to see the cause of death and its causative relationship to the trial.
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Expert opinion in court: Expert to decide on whether the gene editing is an injury or not? Does it amount to grievous hurt?
Key Medicolegal Issues: Ethical and Legal Challenges in CRISPR Technology Implementation
The main key medicolegal issues are as follows
Identity and Forensic DNA: DNA editing could affect paternity and criminal identification, with a change in the STR profile. With DNA editing, a person may end up with two DNA profiles, leading to a chaotic situation.
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Consent and Autonomy: The person allowing this therapy must understand the irreversible and heritable risks. Editing somatic cells affects the patient, while editing embryos, sperm, or eggs will affect future generations.
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Liability and Negligence: If CRISPR cuts the wrong DNA spot, there may be chances of mutations, cancer or a new disease. There will be a question of the standard of care in the court of law. Eugenics and Discrimination: Making selection in the IQ, eye color and height leads to violation of Article 21 of the Constitution of India. As yet, there is no proper legislation in India there may be discrimination in access to CRISPR technology.
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Biosafety and Bioterrorism: CRISPR kits may be misused to create pathogens and may be used as a biological weapon. There may be chances of damage to the ecological system, causing environmental harm. Ownership and patents: There are heavy disputes on the CRISPR patent. There may be medicolegal fights regarding the ownership of profit.
Conclusion
There is a need to have an appropriate legal framework and standard implementation guideline to strengthen the wide application of CRISPR technology. The Forensic experts need to facilitate the formulation of appropriate standard norms. The growing scientific research, strong Indian constitutional commitment to health and evolving national and international policies will facilitate to form robust foundation for future development and advancement.
There is a need for sustained investment in infrastructure development. With appropriate biological oversight and the strategic integration of artificial intelligence, emerging technologies such as CRISPR possess significant potential to revolutionize disease diagnosis, treatment, and precision medicine. It may be further transformed into equitable, real-world benefits to the millions of sufferers of the rare genetic disorders.
Footnotes
Abbreviations
Cas9: CRISPR-associated protein 9.
CRISPR: Clustered Regularly Interspaced Short Palindromic Repeats.
Declaration of Conflict of Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
