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CRISPR-Cas9: Gene-ius of Biotech and a Double-Edged Sword

In 2020, Marwa, a 22-year-old woman, was diagnosed with hypothyroidism, a condition characterised by insufficient thyroid hormone production. Despite being prescribed medication to alleviate her symptoms, she remained trapped in a state of perpetual fatigue and sluggishness.

The year 2021 dealt another blow to Marwa when she was diagnosed with Hashimoto’s thyroiditis, an autoimmune disorder that relentlessly assaults the thyroid gland. This condition stands as the leading cause of hypothyroidism, and, notably, there is no known cure. The prospect of a lifelong battle with Hashimoto’s left Marwa in deep distress.

“I would barely have energy to get out of bed and I felt like a corpse, force-fed to stay alive,’’ Marwa recalled.

However, a ray of hope appeared when Marwa came across CRISPR-Cas9, an innovative gene-editing technology with the potential to combat various diseases, including Hashimoto’s.

“The moment I learnt about CRISPR-Cas9, excitement washed over me. It was almost unbelievable that a cure for Hashimoto’s might actually be within reach. It reignited my hope,” she said.

CRISPR helps in finding the target DNA, while Cas9 acts as the scissor, allowing precise changes. [Natalia Shulga]

 

CRISPR (short for “clustered regularly interspaced short palindromic repeats”) is a technique that allows error correction of genes in the genome, the genetic information warehouse, and enables genes to switch on and off in a quick and affordable manner with relative ease.

CRISPR-Cas9 has two important parts: a guide that finds the DNA you want to change, and a protein called Cas9, which acts just like a scissor. This scissor enables scientists to make changes to the DNA, thus modifying how living things work.

This technology not only offers patients like Marwa hope to confront seemingly incurable ailments but also has the potential and capacity to prove itself as a game-changer in treating various genetic diseases, enhancing crop production, creating disease-resistant strains of crops, and addressing the challenges of feeding a growing global population.

Because of CRISPR-Cas9’s potential, the brilliant minds behind it were honoured with the prestigious Nobel Prize in Chemistry in 2020, further cementing the technology’s reputation as a revolutionary breakthrough in the field of gene editing. However, despite its bright potential, CRISPR-Cas9 faces a lot of backlash because of numerous legal and ethical concerns.

How did we reach here?

In 2005, a group of scientists from the University of California observed mysterious repetitive sequences in the DNA of bacteria, known as CRISPR. These sequences suggested that bacteria could retain genetic “memories” of past viral attacks.

This discovery of bacterial “memory” was a crucial realisation and marked an area of untapped potential that Emmanuelle Charpentier, a French microbiologist and biochemist, and Jennifer Doudna, an American biochemist, joined forces to explore in 2012.

While studying bacteria’s self-defence mechanism, the duo stumbled upon a section of bacterial DNA called CRISPR, a storage unit for tiny snippets of viral DNA. They found out that when bacteria survive a virus attack, they store a piece of the virus’s genetic code in their own DNA. And if the same virus attacks again, the bacteria uses this memory to precisely cut and disable the virus.

Through a series of investigations, Doudna and Charpentier made a groundbreaking discovery of identifying a molecule called Cas9, which in the words of Doudna, acts “as a molecular pair of scissors”- guided by the CRISPR sequences, to precisely cut DNA.

Kashmir and CRISPR

 

A breathtaking aerial view of a paddy field. Amidst changing weather patterns, the agriculture and horticulture sectors face challenges, impacting the livelihoods of thousands in the region. [Safoora Hilal]

 

Jammu and Kashmir has a total area of approximately 430.39 thousand hectares under agriculture and horticulture cultivation. However, over the past few years, the region has been witnessing inconsistent weather patterns affecting the quality and yield of crops.

The horticulture sector in particular has been worst hit because of untimely snowfall and the lowering of import duties on foreign varieties of fruits. More than seven lakh families of around 33 lakh people are associated with this sector and it contributes to over eight per cent of the Gross State Domestic Product (GSDP), bringing in more than 10,000 crores annually.

In a place like Kashmir where the majority of apples are exported, CRISPR-Cas9 presents a promising future for the apple industry, as it can enhance productivity, quality, and crop resilience.

An orchard worker in Kashmir diligently packs apples. The horticulture sector plays a vital role in the region’s economy, supporting over seven lakh families and contributing significantly to the Gross State Domestic Product. [Safoora Hilal]

Javed Ahmed, an Apple orchard owner and a student of science, came across a news story about CRISPR while browsing Facebook. The thought of how it could help him produce better quality apples to face the rising competition from outside immediately came to his mind.

“Most of the Apple trees we plant aren’t that well adapted to Kashmir’s climate and weather patterns, soil composition, or our very high altitude as most of them come from Belgium and France,” says Javid.

Given the impacts of climate change and the absence of a specific precipitation pattern, CRISPR can be used to develop apple varieties that are more resilient to the region’s shifting weather patterns, including temperature fluctuations.

“Modifying the trees specifically to Kashmir can do wonders and can help us stay ahead in the international as well as local markets,” added Javaid.

Roohi Mushtaq, Head of the Department of Biotechnology, S.P. College, says that cutting-edge technologies are expensive, hard to use, and often face delays in reaching and being integrated into less developed regions such as Kashmir, but CRISPR takes the opposite route.

“Despite being a new and powerful technology, CRISPR is affordable and cost-effective, especially in comparison to other gene editing tools. It can be easily integrated into the horticulture sector in Kashmir,” said Roohi

“Such a technology would add value to the Horticulture sector given the substantial scale of horticulture in Kashmir, particularly the apple industry,” she added.

On the research front, Kashmir isn’t lacking either. Research regarding CRISPR-Cas9 is currently being conducted at the Genome Organization Lab in the Department of Biotechnology at the University of Kashmir, under the guidance of Dr. Ajaz Ul Hamid Wani.

“Our primary research focus is on the examination of drosophila (Fruit Flies) wild-type S2 cells. Using the CRISPR-Cas9 technology, our objective is to obtain a deeper understanding of chromosomal configuration and its role in shaping gene expression and developmental processes,’’ says Wardah, research student, at Genome Organization Lab.

Double-Edged Sword

CRISPR’s ethical landscape was put in the spotlight in 2018  when Chinese scientist He Jiankui, edited the genes of twin infants for HIV, raising moral and legal questions about tampering with the genetic makeup of an unborn child incapable of consent.

“Tampering with genetic material could lead to unforeseen long-term consequences, potentially giving rise to complications, including mutations, when these altered genes are employed for reproduction,’’ said Roohi Mushtaq.

However, concerns extend beyond health-related applications, such as altering non-health-related traits like height or athletic ability, giving rise to the controversial notion of “designer babies,” pushing the boundaries of natural genetic diversity.

Striking the right balance between harnessing CRISPR’s potential for medical benefit and implementing the necessary safeguards is essential, as CRISPR-Cas9 sparks profound debates and leaves the future of gene editing poised between hope and uncertainty.

Despite all these concerns and the fact that CRISPR-Cas9 is still in its early stages, people like Marwa have found hope in it.

With her entire future ahead of her, Marwa reiterates, “I believe that it (CRISPR-Cas9) will one day offer a solution for my condition, and it will help me lead a better life.”

Video Link: CRISPR-Cas9 Video
Slideshow Link: CRISPR-Cas9 Slideshow

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