From disruption to delivery: Bridging the gap in the future of CRISPR medicine in India

CRISPR is one of the most disruptive technologies of this century, with a potential impact equivalent to the invention of the internet, semiconductors and AI.¹ It could be transformative in areas as diverse as healthcare, climate and food security. Yet for India to benefit from this innovation, it needs to create the conditions in research, infrastructure, governance and regulation to enable the technology to develop. It must also ensure that issues of cost, equity, safety, ethics and long term impact are addressed.

Promise of therapy in rare disease

In healthcare, CRISPR represents a paradigm shift in the treatment of rare diseases.^2,3 Rather than managing symptoms and treating patients with drugs, CRISPR offers a one-off ‘correction’ to cure a faulty gene. Owing to its programmable nature using a guide RNA, CRISPR offers the possibility of personalised therapy to treat ultra rare diseases and to do so in months compared to years.

The recent report of the first ever personalised CRISPR treatment, used to correct a mutation in the DNA of newborn baby KJ Muldoon has set a new standard for CRISPR therapies.⁴ However, for this success to be scaled up globally, rare-disease policy and research frameworks must be reassessed. Unlike traditional drug development programmes where developers are incentivised to focus on treatments that will help large numbers of patients, a policy for rare disease therapy will need to prioritise equity of access for small populations without prohibitive costs.

A unique opportunity for Indian Pharma

In India, patients suffering from rare diseases form a substantial population spanning 7000–8000 diseases. In this context, India may be best poised to emerge as a new market leader in cell and gene therapy. However, the country’s research efforts have been scattered and a comprehensive national programme is needed to position CRISPR at par with space and AI as a frontier technology.⁵ If India can harness the power of CRISPR under a national policy of indigenous solutions, streamlined supply chains and equitable access, following the tenets of the National Institution for Transforming India (Niti Aayog), it has the potential to lead on healthcare globally.

The Ministry of Health and Family Welfare formulated a National Policy for Treatment of Rare Diseases (NPTRD) in July 2017. Under this policy, diseases are classified into three categories according to the type of treatment available, its cost and the length of the treatment, providing up to INR50 lakhs (£40,000) per patient to subsidise treatment. The third category refers to diseases where small numbers of patients require long-term treatment that is very expensive.⁶ For example, in the US the CRISPR treatment Casgevy (exagamglogene autotemcel) for sickle cell diseases and beta thalassemia is roughly $2 million (£1.47 million) per patient.⁷ The recent case of KJ Muldoon’s therapy was estimated to cost less than $1million, however an accurate figure is hard to obtain because many of those involved worked pro-bono.

The vision is that as cases scale, the costs will reduce. Yet even so, access to such expensive treatments via importing would still render them inaccessible to a majority of patients. The Indian market however, has been steadily maturing for building cell and gene therapy solutions, particularly autologous CAR-T (chimeric antigen receptor T-cells), at a fraction of their price in the US or Europe. India has already demonstrated scientific capability and a path to achieve competitive pricing in developing indigenous autologous CAR-T therapy.

India’s first CRISPR therapy using the enFnCas9 for correcting the sickle cell mutation is also rapidly progressing with researchers at IGIB and AIIMS Delhi ready with all data from preclinical and animal models.⁹ Some preliminary work is ongoing in editing mutations that cause LCA at the LV Prasad Eye Institute.¹⁰

NextCAR19, a product developed by ImmunoAct has been administered in over 350 patients across 70 hospitals until July 2025.¹¹ Soon after Quartemi, CAR-T therapy for non Hodgkin B-CLL is launched. Both these therapies, though not CRISPR based, are approved by CDSCO and available to patients at a cost of INR 30 lakhs (£24,000). Hospitals report INR20–25 lakhs and the intent to go down to INR10–20 lakhs. Although CAR-T treatment does not qualify under the NPTRD’s provision of subsidised treatment, the costs of ~INR30 lakhs is within the NPTRD’s government support of INR50 lakhs, and is a feasible target for cures using gene therapy.

Market opportunity has spurred interest in scaling up both public and private efforts towards developing levers to reduce costs. Apart from patient-specific bespoke manufacturing of the therapy, some of the major drivers of the cost of treatment are the delivery vehicles, viral vectors and clean rooms in GMP facilities, as well as prolonged ICU admission following treatment and logistic requirements such as cold chain shipments.

Balancing time, cost, safety and accuracy

Worldwide, the biggest challenge to bring CRISPR into market is accelerating access without compromising on scientific rigour. All regulatory authorities require robust preclinical data demonstrating high genome-wide specificity assessment for the edit (showing no off-target effects) as well as tissue specificity, no insertional mutagenesis, minimal risk of oncogenesis or disruption of tumor suppressor or essential genes, which must all be evidenced over a long time period.

In the US, the Food and Drug Administration (FDA) recognised that re-evaluation of guidelines were needed to conduct trials in rare diseases, particularly the ultra-rare, where a control arm is often not feasible owing to very small patient populations. In ultra-rare diseases, and n-of-one trials where a particular mutation exists in very few patients, or even just one, conventional control arms are not feasible.¹² The FDA therefore revised the guidelines to accept different trial models. As CRISPR therapy progresses more towards finding cures in n-of-1 cases, newer ways of assessing the effect of a therapy will be needed. These models could be well designed ‘single arm trials’ along with supportive evidence from mechanistic data and natural history.¹³

Suggestions for designing such trials include using the patient’s baseline data before treatment as control, and making use of decentralised data collection and historical real world data (RWD) or even external control data coming from outside trials in place of conventional trial control arms. In future, synthetic controls and even digital twins may be acceptable in such therapy approval guidelines. These moves signal that the FDA recognises the challenges to development of therapy in ultra-rare diseases, particularly n-of-one and it is cautiously expanding to include tailored and more flexible guidelines.

Gene therapy technology has also suffered some recent setbacks, with concerns over liver toxicity in particular. For example, Sarepta’s Elevidys (delandistrogene moxeparvovec), is the first gene therapy approved for Duchenne Muscular Dystrophy (DMD). Though not CRISPR based therapy, the acute liver failure leading to death in certain classes of high-risk patients has raised questions on safety, efficacy and the use of surrogate biomarkers to determine efficacy in trials in place of an actual functional endpoint.¹⁴ As recently as October 2025, Intellia therapeutic paused its CRISPR trials for transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN), following grade 4 liver toxicity observed in a patient.¹⁵ This underscores the importance of a cautious and conservative approach in balancing innovation with patient safety, such as the approach taken in the EU to the adoption of cell and gene therapies.

These events have shaken the investor confidence in gene therapy companies. The pharma and biotech model of high-risk, high-reward one-time gene therapies is being re-evaluated under more conservative safety and regulatory paradigms. Large and mid-size pharma and biotech companies have also scaled back, paused or exited cell- and gene-therapy (CGT) programmes and investor enthusiasm for CRISPR drugs in the pipeline is predicted to diminish.

Supporting innovation responsibly

In a scientific ecosystem that is still evolving, it is important to provide impetus to continue further research and development of therapy. Both the US and EU allow for conditions where a physician can administer an investigational new drug (IND) or provide treatment under a hospital exemption rule provided the treatment is manufactured in GMP compliant standards and administered with physician’s supervision.¹⁶ The challenge to speeding the science for taking CRISPR to the clinics in India is that it does not yet have such a formal hospital exemption pathway. In the current system, even a therapy developed for a single patient requires regulatory approval before administration, unless it’s part of a research study under ICMR guidelines. In the absence of any formal hospital exemption or investigational new drug route, all new therapies would require explicit regulatory oversight, even for a single patient.

However, in October 2025, the Ministry of Health and Family Welfare amended the Drug Rules, 1945, bringing all cell and gene therapy products under direct control of the Drug Controller General of India (DCGI) to regulate and oversee manufacturing, import, GMP compliance and regulatory approval of cell and gene therapy, stem cell products and xenografts.¹⁷

Extra caution and vigilance will be needed in approving new therapies owing to the lack of prior experience and clear frameworks here, and the relative immaturity of the ecosystem. It will require a boost in the national registries and in automation, and centres of excellence must be identified to administer, monitor and follow up on patients to assess the therapy success rate. Even prior to the trials, infrastructure, GMP facilities and rigorous quality control systems in the manufacture of drugs are to be put in place.

Manufacturing and quality control

One of the most critical challenges for India is establishing state-of-the-art manufacturing and quality control for CRISPR therapies. While the pandemic gave a significant boost to India’s bio-manufacturing capability, cell and gene therapies have some unique requirements, such as the RNA oligonucleotides which are at the core of CRISPR therapies. India needs a manufacturer like IDT or Synthego with skills and facilities to meet the stringent requirements of RNA synthesis along with cold chain shipment requirements and QC monitoring at each step. These requirements are expensive to achieve and emerging GMP facilities will need to pay special attention to developing clinical grade RNA oligonucleotides which are at the core of many cell and gene therapy applications including CRISPR. In the recent 2025 amendment that brings manufacturing licenses for cell and gene therapy products under DCGI supervision, the path to application and licenses is now well laid out.¹⁸

Competitive cost is key to India’s success in this field. Domestic manufacturing needs strong support to develop the necessary skillset and the scaling capacity with no compromise on quality. Other costs such as R&D including overheads and regulatory filings, which need to be amortised, must also be addressed. The major costs in bringing a CRISPR therapy to market can be divided into the following components:

Materials: vectors, guide RNA, Cas enzymes, reagents

The key to reaching the INR50 lakhs per patient cost requires various stakeholders to consolidate efforts. In the last five years, it is now well accepted that clinical and molecular grade reagents need to be developed within the Indian ecosystem. The platform for reagent manufacturing for diagnostics (C-CAMP-InDx), that was initially conceived under the guidance of the Principal Scientific Advisor’s office has now expanded to cell and gene therapy reagent manufacturing and building centres of excellence for several key components. Creating domestic supplies of reagents and raw materials is one of the key levers in developing these therapies at an affordable cost.

Hospitals and clinical pipeline for trials

The goal here should be to build a few centers of excellence (CoE) starting with the metros to consolidate the best medical experience, reduce complication rates and shorten length of stay in hospitals. This will facilitate developing consolidated registries, building networks of physicians and using informatics-driven patient recruitment and follow up plans will need to be sharpened. Over time, efficient hub and spoke models can be conceived where manufacturing and GMP can be in centralised facilities while the spoke regional centers can perform the patient infusion and hospital monitoring.

Assembly and manufacturing capacity

Automation in manufacturing and QC requires initial investments, and will have to be introduced early to help build scale.¹⁹ The UK’s Catapult initiative provides a centralised organisation for the country’s cell and gene therapy, acting as a centre of excellence for manufacturing, market launch and other regulatory support, which could serve as a model platform for India to develop CRISPR and other cell and gene therapy products.¹⁹ Initial set up requires both public–private partnership with the government boosting the build-up of such GMP infrastructure facilities and centres of excellence, while the private sector (particularly pharma and vaccine development groups) provide manufacturing and operational excellence. Philanthropic groups and private insurance funders need to work with the government to cover the therapy costs initially.

Carving a niche in IP

The intellectual property space is particularly complex in cell and gene therapy, with CRISPR being the most debated and controversial area. IP battles between top institutes in the world regarding priority and licensing rights have created uncertainty for those hoping to commercialise the technology. In addition, prohibitively expensive IP costs that can completely offset therapy development and affordability, may actually have slowed the development and adoption of this technology. One of the key steps being recognised is to move away from the original SpCas9 still at the heart of the IP battles.

Indian scientists in CSIR have engineered Cas9 isolated from Francisella novicida bacteria (enFnCas9) which has lower specificity and superior off target activity than SpCas9. The patent has been granted in the US and India and presents an opportunity to develop indigenous editing solutions under IP protection, thus providing a relatively clear patent-safe space for developing CRISPR based therapies and running trials in India. Using the enFnCas9, CRISPR therapies in trials for sickle cell disease and for an eye disorder called Leber congenital amaurosis (LCA) are currently in development.

Other countries are also pursuing new approaches to CRISPR and other cell and gene therapies to create a clear IP space. Scientists in Japan have developed unique tools like CRISPR Cas3 that allows deletion of large DNA segments with reduced off-target edits as well as novel approaches to induce multi-exon skipping and to restore dystrophin protein in iPSCs from DMD patients.²¹ Similarly a novel application demonstrated allele-specific multiple chromosome cleavage in Trisomy 21, which could reshape the future of genetic medicine to treat Down Syndrome and other such chromosomal anomalies. South Korea’s CRISPR ecosystem has adopted a platform approach, developing IP for pre-clinical studies.²² India will need to continue innovating and building IP in this space to get into a position of leadership.

A recent report on the CRISPR patent landscape noted that China currently has the highest number of patents filed in CRISPR, with over 10000 patents, followed by the US.²³ The majority of CRISPR patents are in cancer treatments and a significant number use CRISPR as a tool to modify CART, with genetic, neurological and cardiovascular diseases also in the list. While the majority of the patents are held by universities, certain companies have also occupied significant patent space, which is a worthwhile model for India to explore in translating the therapies. For example, Avellino labs has developed proprietary knock-out strategies with a focus on ocular diseases. Toolgen in South Korea has the highest number of patents of any company and has been strategically developing platform IP aiding pre-clinical research.

Ethics of CRISPR therapy

In the wake of the germline editing controversy, when Chinese scientist He Jianku illegally edited the embryos of human twins, the ethics of CRISPR therapy have had global attention. Many countries have explicitly banned human germline editing efforts, including India in its 2017 ICMR guidelines.²⁰

However, the more pressing and complex ethical question that India may need to grapple with is who the intended recipient is and how access to treatment can be made equitable. CRISPR therapies are scientifically universal but economically and logistically asymmetric, the challenges differ sharply between developed and developing countries. The key contrasts are summarised in Table 1, covering issues of equity, safety and sustainability.

Accordingly, the Rare Disease Policy and the Government’s current provision to subsidize treatments up to INR50 lakhs should define the upper limit for the cost of CRISPR-based therapies in India. Positioning this price ceiling within the national health strategy not only anchors the technology in a sustainable economic model but also signals India’s intent to make advanced therapeutics financially accessible to patients with rare and severe conditions.

The rise of CRISPR therapies under the wider framework of cell and gene therapy presents a transformative opportunity for India, but it also requires coordinated efforts from researchers, clinicians and policymakers to ensure these innovations become accessible and affordable.