Kashmir: Gene-Editing A Life

   

A little over 13 years after the birth of Noori, India’s first cloned Pashmina goat, cloning pioneer Dr Riyaz A Shah has once again made history—this time by leading a team of scientists at SKUAST to engineer the country’s first gene-edited sheep. Syed Shadab Ali Gillani reports on the arduous journey behind this rare scientific breakthrough

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In a pioneering breakthrough, Kashmiri scientists at Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir (SKUAST-K) have created India’s first gene-edited sheep using CRISPR-Cas9 technology. The lamb was born at the university’s Faculty of Veterinary Sciences, Shuhama campus, marking a milestone in the country’s advancement in animal biotechnology.

The project was led by Dr Riaz Ahmad Shah, the Kashmir scientist who pioneered animal cloning in India. He first cloned India’s first buffalo calf, Garima, at the National Dairy Research Institute in Karnal as part of his PhD in 2009. In 2012, at SKUAST-K, he cloned the world’s first Pashmina goat, Noori. Now, as head of SKUAST’s Animal Biotechnology division and Dean of the Faculty of Veterinary Sciences, he led the project that led to the birth of the first gene-edited sheep.

Dr Suhail Magray, a key researcher on the team, however, clarified that cloning and gene editing are distinct technologies. Cloning, he explained, is akin to producing an exact genetic copy of an animal, much like photocopying a book. In contrast, gene editing targets specific changes within the DNA sequence, similar to editing a line in a book. He described this development as a major scientific achievement.

“This is not just the birth of a lamb, but the beginning of a new era in livestock genetics,” said Varsity Vice-Chancellor Dr Nazir Ahmad Ganai. Gene editing, he asserted, enables precise, beneficial changes without introducing foreign DNA, making the process safer, more efficient, and potentially more acceptable under India’s evolving biotechnology regulations.

Six Years of Struggle

The unnamed sheep’s birth is a long story. The project began more than six years ago with funding from the Indian Council of Agricultural Research (ICAR). It built upon the university’s earlier expertise in cloning, embryo transfer, and assisted reproductive technologies.

“The targeted change was made in the myostatin gene,” said Prof Shah. This gene, responsible for regulating muscle growth, is naturally inactive in some European breeds such as Texel, resulting in a 30 per cent increase in muscle mass. Through CRISPR-Cas9, the team achieved a precise edit to deactivate the gene in a local breed.

CRISPR-Cas9, a tool for genome editing, allows scientists to make targeted alterations without adding foreign genetic material. This crucial difference separates gene editing from genetically modified organisms (GMOs) and influences both regulatory classification and public perception, scientists said.

Explaining the process, Dr Shah said the work began with collecting embryos from donor sheep. The CRISPR-Cas9 complex was introduced into the embryos under sterile conditions. These were then cultured in controlled laboratory settings before being transferred to a recipient ewe.

Two lambs were born from the single recipient female. Of the two, only one carried the edited MSTN gene. At birth, there were no visible physical differences between the gene-edited lamb and the non-edited one. Edits made at the embryonic level usually do not show immediate traits. Molecular diagnostics, including polymerase chain reaction (PCR) and DNA sequencing, later confirmed the presence of the desired gene edit in one of the lambs.

Cutting-Edge Cloning

Both lambs are female. Regular observations are being conducted to document their growth rate parameters.

A study titled Global Status of Gene-Edited Animals for Agricultural Applications by Alba V. Ledesma and Alison L. Van Eenennaam defines gene editing as the use of a site-directed nuclease to create a precise break in DNA at a targeted location. The authors recall that genetically engineered livestock was first reported in 1985, involving the insertion of recombinant DNA at random sites to produce genetically modified organisms (GMOs). Despite decades of progress, only two GMO animal products, the AquAdvantage salmon and GalSafe pig, have been approved for food. The slow commercialisation is attributed to time-consuming and costly regulatory processes in most countries.

Discussing the project, Dr Suhail explained that the team had targeted the myostatin gene, which regulates muscle growth. Using CRISPR-Cas9, the gene-editing tool that earned the Nobel Prize in Chemistry in 2020, they introduced precise edits into sheep embryos. These embryos were cultivated in the laboratory before being implanted into surrogate ewes. Of the resulting offspring, one was confirmed as gene-edited following DNA sequencing.

Dr Suhail added that to establish statistically significant data, they aimed to produce more such animals and monitor them over time. The work, he said, was strictly for research purposes, given the absence of specific regulations for gene-edited animals in India. Around the world, gene editing has already been used to develop disease-resistant animals and to address genetic disorders in humans. Unlike transgenic organisms, he noted, no foreign DNA was introduced in this case. The disruption of the myostatin gene occurs naturally in some breeds known for increased muscle mass. The team had merely edited the gene precisely at the intended site to demonstrate their capability.

Laboratory of Innovation

The gene-editing work was carried out at SKUAST-K’s Advanced Centre for Reproductive Biotechnology. The facility is equipped with microinjection stations, CO₂ incubators, thermo-cyclers, electrophoresis systems, and embryo culture units.

Developed during the Noori cloning project, the laboratory has dedicated sections for embryo handling, manipulation, incubation, and molecular work. Its systems were sourced through various research phases. The facility has become a reference point for other institutions and has helped establish similar setups, including one by the Sheep Husbandry Department in Kashmir.

The team now aims to expand the research by developing a group of genetically edited animals for further studies. All efforts, Dr Suhail said, remained focused on one project at a time to ensure clear direction and continuity.

Precision and Protocol

The research team comprised embryologists, molecular biologists, veterinary scientists, and technical staff. All personnel were trained in gene-editing protocols through national and international collaborations. Standard operating procedures were followed meticulously at every stage – from embryo and ovum collection to fertilisation, gene editing, embryo culture, and transfer.

All experimental protocols were reviewed and approved by the Institutional Biosafety Committee and the Institutional Animal Ethics Committee of SKUAST-K.

India’s first gene-edited sheep born at SKUAST-K

Policy Framework

India currently lacks a specific regulatory framework for gene-edited livestock. The existing rules under the Genetic Engineering Appraisal Committee (GEAC) applied mainly to genetically modified crops. These involved transgenes, the insertion of foreign genes, whereas gene editing modified existing genes without introducing external DNA.

This distinction held significant implications for both policy and public perception. As the lamb engineered by SKUAST-K is gene-edited and not genetically modified, it might be categorised differently, pending the introduction of national guidelines for genome-edited organisms.

Discussions are ongoing at the central level to draft comprehensive regulations that would distinguish gene editing from transgenesis. The SKUAST-K project could serve as a model for evaluating such technologies within India’s evolving biotechnology policy.

Scientific Excellence

The gene-edited sheep project formed part of SKUAST-K’s broader ambition to emerge as a centre of excellence in reproductive biotechnology. Vice-Chancellor Dr Nazir Ahmad Ganai said the university aimed to develop infrastructure supporting advanced research in livestock breeding, molecular genetics, and biotechnology.

Dr Riaz Ahmad Shah has played a central role in the university’s biotechnology programme for over a decade. His earlier work had focused on in vitro fertilisation, embryo preservation, and cloning technologies.

The university was now planning to extend gene-editing research to other livestock species, including goats and poultry. Proposals are being prepared to secure funding for these initiatives.

The primary objective of the current project was to establish proof of concept for gene-editing livestock using CRISPR technology within the Indian context. The successful birth of the edited lamb confirmed the technical feasibility of such research under domestic conditions.

Further studies would assess the reproductive performance, health, and economic value of the gene-edited animals. The team intends to explore editing genes linked to disease resistance, climate tolerance, and reproductive efficiency.

At present, the research remains limited to laboratory and institutional settings. Any application at the farm level would depend on national policy decisions and regulatory approval.

The development of gene-edited sheep by SKUAST-K marked a significant advance in the use of genome editing in livestock. By achieving this without introducing foreign DNA, the university laid the groundwork for localised genetic interventions in animal breeding.

The project aligned with national priorities on food security, livestock productivity, and scientific innovation. Its success pointed towards the potential for broader genome editing research under India’s biotechnology roadmap, subject to regulatory clarity and sustained institutional support.

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