Clustered Regularly Interspaced Short Palindromic Repeats, popularly referred to by its acronym CRISPR or CRISPR/Cas9, is a simple yet powerful gene editing technology that allows making specific changes (addition, modifications and deletions) in the DNA of humans, animals and plants, thereby offering tremendous potential in a wide array of applications ranging from agricultural biotechnology to disease therapeutics. Moreover, CRISPR is able to serve a dual function of engineering specific DNA and serving as functional screens in order to identify genes involved in a phenotype of interest.

CRISPR consists of two key components, a guide RNA (gRNA) and a non-specific CRISPR-associated endonuclease (Cas9). The gRNA is essentially a pre-designed synthetic RNA (~20 base pair long) composed of the CRISPR RNA (crRNA) and the trans-activated crRNA (trRNA), which not only simplifies the workflow of the CRISPR experiments, but also guides the Cas9 endonucleases to make desired edits at specific genomic locations. As the gRNA-Cas9 complex is guided to the unique target DNA sequence in the target cell, the Cas9 endonuclease cleaves the DNA if there is a sufficient match between the gRNA and the target sequence within the cell.

Following CRISPR gene modification, techniques such as NGS and droplet digital PCR (ddPCR) must be applied to analyze and confirm results of the gene modifications. NGS and ddPCR also provide the basis for understanding cellular gene sequences before specific CRISPR modifications can be proposed. Such analysis thereby permits the application of CRISPR/Cas9 technology to a large number of tissue and cell types, starting with stable cell lines, and progressing all the way to stem cells, or even in real time, patient-derived cancer cells. In addition, gene delivery tools such as transfection systems or retroviruses, plasmids, expression vectors and bioinformatic tools are also utilized in a complementary manner for targeted delivery, designing gRNAs and conducting CRISPR experiments.

Due to the relative simplicity and flexibility of the CRISPR/Cas9 technology, it has been widely used in various applications in academia, biotechnology, pharmaceuticals and applied markets. Some prominent applications of the CRISPR/Cas9 technology include disease research, development of model organisms, drug identification/validation, gene therapy, stem cell research, agricultural biotechnology and CRISPR-based therapeutics.

The market for CRISPR products is growing at a staggeringly high rate, being driven by rapidly increasing adoption for translational research and therapeutic applications. Currently, the market for CRISPR alone constitutes close to two-thirds of the total gene editing assay market, and is forecasted to grow more than 30% in 2018. This growth can be attributed to the improved funding for CRISPR-based research by the NIH and other organizations, along with a constantly growing use of CRISPR tools by CROs in order to produce genetically engineered mice for research purposes. Recently trending developments in the technology involve the requirement of two binding events (proximal-CRISPR), or combining CRISPR with other technologies such as Zinc-Finger Nucleases (ZFN) and RNA interference (RNAi) in order to increase CRISPR’s accuracy and reduce its off-target effects. This will further bolster the market growth.

Addgene is a nonprofit organization that offers a plasmid repository for scientists to use and share, thereby being one of the most prominent suppliers of such products. Thermo Fisher Scientific is the leading commercial vendor in the CRISPR market with its GeneArt CRISPR series of various product tools ranging from nuclease mRNA to all-in-one plasmid kits. MilliporeSigma is another leading supplier in this market, thanks to its product offerings that include positive control plasmids, Cas9 nickase mRNA and CRISPR lentiviral tools.

Some of the other vendors in the CRISPR market also provide unique animal models, cell lines, stem cells and other CRISPR-based research tools. Other significant vendors in the market include Agilent Technologies, Dharmacon (GE Healthcare) (see Executive Briefing), Horizon Discovery, Integrated DNA Technologies (IDT), Jackson Laboratory and Origene.

CRISPR/Cas9 at a Glance:

Leading Vendors:

• Addgene
• Thermo Fisher Scientific
• MilliporeSigma

Largest Markets:

• Academia
• Biotechnology
• Pharmaceuticals

Product Cost:

• $100–$1,000 (gRNA, expression libraries and assay kits)
• $1,200–$1,800 (cell lines)