28 June 2017
CM Industrial By CM LifeScience

An Introduction to CRISPR-Cas9.

Until very recently, the most talked about and desirable technology within molecular biology was Next Generation Sequencing (NGS). NGS was the technology sales reps wanted to sell and molecular biologists wanted to work with. Recently though, that’s changed with the arrival of CRISPR Cas9.

CRISPR is the hottest topic in molecular biology and more specifically in genome engineering, especially as we see it become commercialised and approved by the US and UK governments for use in human embryo’s and adults. So, what’s all the fuss about?!  I’ll do my best to take a look at the CRISPR frenzy and what I think the future holds for it.

CRISPR’s Superiority

The technology to edit genes has been around for years with popular methods such as RNAi, Zinc Finger Nucleases and TALENS at the heart of gene engineering. However, the speed, cost and efficiency at which CRISPR-Cas9 operates is truly unprecedented, and simply put, miles ahead of the competition.

Before the emergence of CRISPR, RNAi was the most popular choice for scientists to edit genes. The main limitation was temporary inhibition of gene functionality and unpredictable off-target effects – costly mistakes for costly reagents.

The CRISPR-Cas9 system breaks down into; CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat) where all the action takes place (replaced by a Synthetic guide RNA), and Cas9, the ‘search and destroy’ Endonuclease Enzyme (figure 1). Working as a tag team, the Cas9 enzyme analyses the cell's genome to identify matching genomic sequence, then slices the DNA in the cell’s enzymes. DNA can then be added/modified within the cell at the desired site – Voilà, edited genome. 

Figure 1 – CRISPR-Cas9 mechanism 

The simplicity, specificity and cost-efficiency of the CRISPR Cas9 system is what will solidify its candidacy for genome editing for years to come.

CRISPR's Value

Since its inception in 2012, CRISPR has already revolutionised the precision genome engineering market as we know it. Revenues are expected to hit $7.5B USD by 2024, with a 14.7% CAGR. 

The money will be generated from either conventional sales of CRISPR enabling products, licencing fees for using CRISPR in house to manufacture therapeutics/therapies and of course companies filing for IPO’s. 

As with any exciting new technology entering the market, competition is heated; early players are gaining momentum and new comers are trying to claim superiority in their adoption of the technology. Now let’s take a look at who’s doing what.

#CRISPR & Trending

CRISPR’s versatility has allowed adoption by biotechnology and bio-pharmaceutical companies across wide target applications including research, therapeutic and agriculture.

Here’s a few companies to keep an eye on in the current landscape:


Main application of CRISPR as a service to genetically modify crops and seeds for sale in the global agricultural sector:

DuPont Pioneer, Monsanto, Caribou Biosciences, Syngenta


Main adoption is to manufacture products/kits to support CRISPR workflows including Synthetic crRNA, tracrRNA, modified Cas9 endonucleases, and genetically defined Cell lines for drug discovery:

GE Dharmacon, MilliporeSigma, Cellectis, Synthego, Thermo Fisher (GeneArt), Cellular Dynamics International, Horizon Discovery 


In house use of CRISPR to manufacturer personalised therapeutics and targeted gene/cell therapies:

CRISPR Therapeutics, Editas Medicine, Intellia Therapeutics, Caribou Biosciences

There are additional exciting new start-ups coming to market every other day trying to enter the CRISPR race. This is making the industry even more exciting for candidates all over the world who are assessing their next career move.

Battle Of The Patents

In addition to the companies battling for market share in the wider CRISPR space, there’s also a huge amount of competition going on for exclusive patent ownership of CRISPR itself. Given the commercial explosion we’ve seen in CRISPR, this is a battle worth fighting as the victor could be in line for billions in licensing fees and royalties.

There are 2 opposing institutions locking horns; UC Berkeley and the Broad Institute, consisting of Harvard and MIT.

Both have justifiable claims to fame with Jennifer Doudna and Emmanuelle Charpentier, 2 leading biochemists from UC Berkeley, publishing the first Science paper in 2012 highlighting CRISPR’s ability to edit DNA in the lab. This publication allowed them to take credit for proving that CRISPR could be used to alter all genes in prokaryotic cells. 

In 2013 Feng Zhang, a leading Molecular Biologist from the broad institute, was the first to successfully adapt CRISPR-Cas9 for genome editing specifically in eukaryotic (animal & human) cells. Patents were filed for CRISPR for both prokaryotic and eukaryotic uses, but Zhang’s later patent, filed in 2014, was more specific. 

Head to Head: Jennifer Doudna and Feng Zhang

This means that, as it stands, the Broad Institute owns the patent for using CRISPR on human and animal genome editing – which is, and will continue to be, an extremely profitable market.

Berkeley are disputing the decision to award this patent, and the case is currently with a federal court in the US.

We’re still waiting to see who manages to land the final gene knockout blow (no pun intended), but it’s a fascinating watch as it stands. 

CRISPR’s Future And Potential Hurdles

Regardless of the outcome of the legal battle, the result is that we are now seeing CRISPR being used in human genome editing, which is raising some questions over the ethical and moral implications of the technology. We’ve recently, seen a significant breakthrough in the development of ‘designer babies’ after embryos were edited with CRISPR in China.

Legislation and stringent regulations will, and are, being introduced for all commercial scientists to adhere to, but as the technology becomes more widely adopted and companies acquire more expertise in this space, we could see even more breakthroughs, including the potential to alleviate devastating genetic disorders and potentially start to contribute to helping with problems as monumental as world hunger.

So, CRISPR is a hyper-profitable new technology which could cure disease, world hunger and make companies billions of dollars in the process, but it will be exciting to see where the next application of CRISPR comes from, and what happens next for the tech.


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