Genome Editing: The Key to Personalized Health and Beyond

Introduction

• The Government has allowed genome-edited plants without the cumbersome GMO (Genetically Modified Organisms) regulation at the Genetic Engineering Appraisal Committee (GEAC).
• The government has exempted Site Directed Nuclease (SDN) 1 and 2 genomes from Rules 7-11 of the Environment Protection Act, thus allowing it to avoid a long process for approval of GM crops through the Genetic Engineering Appraisal Committee (GEAC).
• The Institutional BioSafety Committee (IBSC) under the Environment Protection Act would now be entrusted to certify that the genome edited crop is devoid of any foreign DNA.

Genome Editing

• Genome editing (also called gene editing) is a group of technologies that give scientists the ability to change an organism’s Deoxy-Ribonucleic Acid (DNA).
• These technologies allow genetic material to be added, removed, or altered at particular locations in the genome.
• Advanced research has allowed scientists to develop the highly effective Clustered Regularly Interspaced Palindromic Repeat (CRISPR) -associated proteins based systems. This system allows for targeted intervention at the genome sequence.
• This tool has opened up various possibilities in plant breeding. Using this tool, agricultural scientists can now edit the genome to insert specific traits in the gene sequence.
• Depending on the nature of the edit that is carried out, the process is divided into three categories — SDN 1, SDN 2 and SDN 3.
• Site Directed Nuclease (SDN) 1 introduces changes in the host genome’s DNA through small insertions/deletions without introduction of foreign genetic material.
• In SDN 2, the edit involves using a small DNA template to generate specific changes. Both these processes do not involve alien genetic material and the end result is indistinguishable from conventionally bred crop varieties.
• The SDN3 process involves larger DNA elements or full length genes of foreign origin which makes it similar to Genetically modified organisms (GMO) development.

Difference Between Gene Editing & GMO development

• Genetically Modified Organisms (GMO) involves modification of the genetic material of the host by introduction of a foreign genetic material.
• In the case of agriculture, soil bacteria is the best mining source for such genes which are then inserted into the host genome using genetic engineering.
• For example, in case of cotton, introduction of genes cry1Ac and cry2Ab mined from the soil bacterium Bacillus Thuringiensis (BT) allow the native cotton plant to generate endotoxins to fight pink bollworm naturally.
• BT Cotton uses this advantage to help farmers naturally fight pink bollworm which is the most common pest for cotton farmers.
• The basic difference between genome editing and genetic engineering is that while the former does not involve the introduction of foreign genetic material, the latter does.
• In the case of agriculture, both the techniques aim to generate variants which are better yielding and more resistant to biotic and abiotic stress.
• Before the advent of genetic engineering, such variety improvement was done through selective breeding which involved carefully crossing plants with specific traits to produce the desired trait in the offspring.
• Genetic engineering has not only made this work more accurate but has also allowed scientists to have greater control on trait development.

Need for Human Genome Editing

• Increasing Genetic disorders: India is considered as the “Pandora’s Box of genetic disorders. India has a high prevalence of rare recessive genetic diseases due to its population’s heterogeneity and inbreeding rates. Human genome editing could potentially address this issue by correcting or eliminating disease-causing mutations in affected individuals or preventing the transmission of these mutations to future generations.
• Rising incidence of viral disease: According to the World Health Organization, an estimated 2.1 million people in India were living with HIV in 2019, with a prevalence rate of 0.2.
• Cancer as a growing health concern:  According to The Report of National Cancer Registry Programme, 2020 India’s cancer burden could increase from 1.39 million during this year to 1.57 million in 2025. Human gene editing can address this burden.
• Growing concerns about treatment side effects: Genome editing can be utilized to develop tailored therapy based on a person’s particular genetic make-up. This might result in medicines that are more effective and efficient and have fewer negative effects. 
• Increasing food allergies: The incidence of food allergies among Indian children is thought to be between 6-8%, according to a study that was published in the Indian Journal of Pediatrics. Foods free of allergies can also be produced via human gene editing. 

Regulatory Issues Preventing the Technique

• Across the world, GM crops have been a topic of debate, with many environmentalists opposing it on the grounds of bio safety and incomplete data. In India, the introduction of GM crops is a laborious process which involves multiple levels of checks.
• Till date the only crop which has crossed the regulatory red tape is Bt cotton.
• Scientists both in India and across the world have been quick to draw the line between GM crops and genome edited crops. The latter, they have pointed out, has no foreign genetic material in them which makes them indistinguishable from traditional hybrids.
• Globally, European Union countries have bracketed genome edited crops with GM crops. Countries like Argentina, Israel, US, Canada, etc have liberal regulations for genome edited crops.

Advantages

• Potential cures for genetic diseases: Genetic illnesses that may be cured by genome editing include those for which there are no viable treatments at the moment. For instance, curing cystic fibrosis might include employing genome editing to fix the genetic mutation that causes the condition. 
• Can treat cancer diseases: Human gene editing has the potential to improve the precision and efficacy of cancer models, which is essential for the development of cancer therapeutics. For instance, The Cancer Genome Atlas (TCGA), a cancer genomics initiative in the US, has already mapped the genomic variations in 33 different cancer types in an effort to enhance cancer treatment.
• Can treat viral diseases:  Human genome editing has the potential to treat viral illnesses by altering the patient’s own immune cells to more effectively target and eradicate the virus. One strategy is to utilize CRISPR-Cas9 to modify the immune cell type T cells’ DNA such that they are immune to HIV infection. Another strategy is to employ CRISPR-Cas9 to eradicate the hepatitis B virus from liver cells that have been infected.
• Increased understanding of the human genome: Investigating the results of altering particular genes may aid research into the function of those genes in health and disease. 
• Scientific advancements: Genome editing can be used to produce animal models of human diseases, helping researchers better understand these conditions and come up with new treatments. 
• Enhanced biosecurity: By using genome editing to create disease-resistant animals, zoonotic disease transmission can be stopped.  
• Increasing agricultural production and food security: Crops that are more pest-resistant, thirstier, or more nutrient-dense might be created by genome editing, which would enhance agricultural output. It’s important to remember that while genome editing may have certain benefits, there are also significant ethical and safety issues that need to be carefully explored before the technique is used widely.

Challenges

• Ethical concerns: Ethics-related issues include whether it is appropriate to employ gene editing to modify features unrelated to disease or to genetically engineered embryos. For example, altering genes to increase intelligence or physical attractiveness can have unforeseen repercussions and worsen societal inequality.
• Genome editing and “designer babies”: There are worries that “designer babies” may be produced for social rather than medical purposes. This poses moral questions and may result in the emergence of a genetically modified aristocracy. For instance, altering an embryo’s genes to boost intelligence could result in a technological divide in society between those who have access to it and those who do not. 
• Off-target effects: Gene editing may unintentionally affect genes other than the one it is intended to, with unanticipated results. For instance, a 2017 study found that CRISPR-Cas9 gene editing led to unanticipated mouse alterations.  
• Safety concerns: Gene editing may have unforeseen effects, such as immunological reactions or off-target effects, which could endanger the health of the person receiving the process. For instance, altering the incorrect gene may result in cancer. 
• Germline editing: Up to this point, all therapeutic genome editing procedures in humans have been carried out in somatic cells (i.e., only the patient is impacted; there is no likelihood that the patient’s kids will inherit the altered genes).
• However, altering the germline may result in unforeseen changes that are inherited by subsequent generations. Safety and ethical issues are brought up by this. For instance, altering a human embryo’s genes can have unexpected genetic effects that can be passed on to progeny.  
• Lack of long-term data: There is concern that changes made to a person’s DNA could have unforeseen effects that wouldn’t become apparent for years or even decades. The long-term impacts of gene editing are also not well understood. For instance, employing CRISPR to remove a specific disease-causing gene may have unintended implications that are not yet fully understood.  
• Challenges with regulation: Currently, there is no regulatory organization to monitor the usage and applications of human genome editing technology. As a result, it might result in less transparency, poor quality, and increased needless delays in patient care.
• Ecological impacts: Gene drives can be used to propagate a set of genes with negative traits throughout a population, which can lead to severe ecological consequences. For example, introducing gene-edited mosquitoes that are resistant to malaria could lead to the elimination of the mosquito population, which could disrupt the ecosystem. 
• Uncontrolled clinical trials: There are currently no standard norms for clinical trials to check the efficacy of genome editing treatment. This can lead to uncontrolled clinical trials, which can result in patients receiving ineffective or potentially harmful treatments. 

Way Forward

• Continued Research: More study is required to properly comprehend the possible advantages and dangers of changing the human genome. This includes extensive investigations into the security and effectiveness of various gene editing methods as well as examinations into the moral, societal, and legal ramifications of the technology. 
• Responsible Use: Human genome editing must be used in an ethical and responsible manner, under proper regulation and supervision. Among other things, this entails making sure the technology is exclusively applied for medical requirements and that it does not increase already-existing disparities. 
• Collaboration and transparency: To guarantee that human genome editing is used responsibly and transparently, collaboration between scientists, politicians, and the general public is crucial. This entails open discussion of the technology’s possible advantages and disadvantages as well as interaction with the general public on important moral and legal matters. 
• Establishment of ethical principles: To guarantee that human genome editing is utilized responsibly and ethically, it is crucial to establish firm ethical principles. The rules cover topics like modifying germline cells, using gene editing for non-medical objectives, and obtaining the informed consent of those undergoing the process. 
• Infrastructure investment: To facilitate the development and application of gene editing technologies, infrastructure investment is required. This entails funding for research facilities, oversight organizations, and public health programs as well as the creation of global standards and guidelines for the application of gene editing. 
• Educate the public: Information about the ethical and societal ramifications, potential advantages, and risks of human genome editing should be made available to the general public. This can assist in ensuring that accurate and current information is used to inform public opinion and policy decisions. 

FAQs

1. Is Genome Editing safe for humans?
   Genome Editing holds great promise, but safety is a top concern. Rigorous testing and ethical guidelines are crucial to ensure its safety.
2. Can Genome Editing cure all genetic diseases?
   While it shows potential, not all genetic diseases can be cured through Genome Editing. Research is ongoing to expand its applications.
3. What are the ethical concerns surrounding Genome Editing?
   Ethical concerns include the potential for designer babies, unintended consequences, and the long-term effects of genetic modifications.
4. Are there any legal regulations for Genome Editing?
   Many countries have regulations in place to govern Genome Editing, with an emphasis on ethical use and safety.
5. How can Genome Editing benefit agriculture and the environment?
   Genome Editing can enhance crop resilience, nutritional value, and sustainability. It also aids conservation efforts by preserving endangered species.

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