#UndertheScope: CRISPR - Decoding Genetic Potential

Welcome to the third issue of #UndertheScope, Gilbert Meher Science's monthly newsletter designed to bring communities together in Science.

In this issue, we will delve into the ever-evolving world of #CRISPR. We are joined by Ross Bundy, entrepreneur and CEO of CRISPR QC, an organisation that have developed the world's first CRISPR Analytics Platform.

CRISPR, and the broader field of #geneediting, stand at the forefront of current discussions surrounding scientific innovation and its potential applications.

With Ross' insight, we aim to provide an insight into CRISPR technology, outlining its potential and accompanying risks, alongside providing some of Ross' advice on how to succeed in such a challenging industry.

?? CRISPR (Cluster Regularly Interspace Short Palindromic Repeats) is a gene-editing technology using #Cas9 to target specific genes, enabling scientists to modify #DNA sequences with precision.

The tool, for which Jennifer Doudna and Emmanuelle Charpentier won the Nobel Prize in Chemistry,?has the potential to revolutionize various fields. Impacting medicine and agriculture, it enables precise modifications to genetic material and offers unprecedented opportunities for research, disease treatment, and #geneticengineering.?

?? The Transformative Power of CRISPR

Despite being a relatively new technology, CRISPR has already demonstrated great potential to revolutionize innovation in Science.?

"Gene editing has the capability to impact billions of people by improving economics of third world countries, and enabling accelerated research into diseases." - Ross Bundy

Some positive impacts of CRISPR include:

• Its precision capabilities allow scientists to make accurate modifications in DNA sequences, opening up new avenues to treating genetic diseases and developing personalized therapies.
• It serves as a powerful tool for #diseasemodelling and gene function studies.
• Potential applications in conservation and ecosystem restoration.
• Amongst broader genome editing technologies, CRISPR is often considered to be advantageous thanks to it being relatively easy to handle, high accuracy and low cost.

Included amongst its early success stories is the recent FDA approval for the use of CRISPR to correct the genetic defect causing #sicklecelldisease.

?? Navigating the Risks and Ethical Dilemmas

However, while CRISPR offers significant capabilities, it also raises ethical and societal considerations. The responsible and regulated use of CRISPR technology is key to its success.

Regulatory challenges of the start-up world:

The increased pace of scientific discoveries and technological advances in recent decades has posed novel challenges for regulators. Currently, the FDA considers any use of CRISPR in humans to be gene therapy, and gene therapy products are regulated by the system that is traditionally applied to biologics.

The rapid development of CRISPR and Gene Editing has outpaced the establishment of specific regulatory systems, which could lead to inconsistent or inadequate oversight.

Ross describes CRISPR and Cell/Gene Editing as an entrepreneurial space – a market in which everyone is racing to ‘be the first’, get funding and drive their stock prices up. As is typical in the #biotechnology start-up world, scientific innovation is the driving factor, deprioritising the safety or precision of the therapy.

“Of course the biotech organisations want to do right by patients, but the reality is start-ups can’t raise money on being safe. If the FDA hasn’t caught up yet, it’s not in a start-up’s interests to focus on safety, when your stock price or valuation is directly correlated to how quickly you get to trials.” – Ross Bundy

Science without regulation comes with risks – are the therapeutics currently in trial reproducible or even safe for wider use?

Immune response:

It goes without saying that the science is complex. Introducing CRISPR components into the body could trigger an immune reaction, as the body may recognize them as foreign invaders. This immune reaction might limit the effectiveness of the treatment or cause adverse reactions.

"Everybody's DNA is different! We already know that different drugs apply differently to different ethnicities, due to varying genomic profiles." - Ross Bundy

Unintended consequences: Modifying genes could have unforeseen effects on the overall functioning of an organism or its interactions with the environment.

Equity and access:

CRISPR-based therapeutics usually cost in the region of $1million for a single therapy, and the three most expensive drugs in the world were all gene therapies in 2023.

"One of the key issues with Cell and Gene Therapy is the price. Pricing needs to be accessible to broad populations in order to be able to cure people." - Ross Bundy

Ethical dilemmas: Changing the body's DNA inevitably raies ethical concerns - should it be applied to enhance basic human traits like height or intelligence? Who decides which traits are considered a disability or disorder (and therefore should be treated)? Jennifer Doudna herself warned of the unknown consequences of embryo editing.

?? Scaling New Heights: Evaluating the Scalability Potential of the CRISPR Industry

The National Library of Medicine's CRISPR Journal outlines that scalability issues are preventing CRISPR from reaching its full potential in healthcare, industrial, and agricultural industries.

"CRISPR’s value is derived from the cell itself – the ability to make a cell, with the right DNA, in a specific way. Without control over process this ability becomes difficult, and is certainly not scalable." - Ross Bundy

Other limitations in the scalability of the CRISPR industry include:

• The race to innovation. According to market factors, the value of biotech companies who are developing cell and gene therapies is derived by how quickly they get to trial. Speed and quality control/scalability do not always go hand in hand.
• DNA. If a therapeutic can react differently depending on DNA, and every patient’s DNA is different, how can you prove safety across a mass group of patients? Does it need to be proven that each individual therapy is safe for each individual patient before its use?
• Slow regulatory systems. It’s been well-documented that the FDA has been struggling to keep up with the volume of gene and cell therapy submissions. As they simultaneously develop a new dedicated regulatory framework, there is concern that, once the new framework is released, organisations will have to go back and redo elements of the process, slowing down commercial launch.
• Business challenges. Some of these challenges are high R&D costs, the lengthy process of obtaining IP rights and patents, and the potential for legal conflicts and liabilities.
• Limited target applications. As of now, CRISPR technology's applications are not fully realized across all possible genetic targets. Expanding the range of treatable diseases and conditions is essential for maximizing the technology's potential impact and scalability.

Addressing these scalability challenges will be crucial for the CRISPR industry to fulfil its potential in revolutionizing, agriculture, and various other fields.

?? A Glimpse into Tomorrow

CRISPR offers huge potential across various domains. It holds the promise of #targetedtherapies, precise gene editing, and personalised treatments. It holds the ability to accelerate the development of innovative treatments, facilitates disease modelling, and even holds potential for conservation efforts. But are we getting ahead of ourselves??

"We must remain grounded. Rather than getting caught up in the 'hype' of what CRISPR can do, we need to focus on what can realistically be achieved in the here and now." - Ross Bundy

Ross Bundy suggests:

1. Establish a well-designed and solid foundation in CRISPR.
2. Introduction of industry-wide standards for pricing, regulations, and product development.
3. Don't get caught up in the hype: It's important that the industry stays grounded and focuses on what can realistically be achieved in the here and now.

?? CRISPR QC: The World's First and Only CRISPR Analytics Platform

With a lucrative background in Finance and Manufacturing, Ross Bundy ventured into the world of Science just over 10 years ago to support the commercialisation of a graphene biosensor organisation.

Fast forward to 2021, he is now the Co-Founder and CEO of CRISPR QC - an organisation that has developed the world's first and only CRISPR Analytics Platform.

CRISPR QC aims to maximise gene editing's potential by offering advanced quality control metrics and predictive insights. As they stated - "empowering Scientists at the forefront of the gene editing revolution with the insights needed to realize the full potential of CRISPR."

The journey of gene editing is just beginning, and as it unfolds, it promises to reshape the landscape of science, medicine, and beyond...

?? Join the conversation:

• How do you envision the future of CRISPR?
• What are your thoughts on its ethical implications?

Share your insights, questions, and perspectives with us!

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