CRISPR Can Do More Than Gene Editing
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is best known as a tool for genetic engineering and more recently curing genetic diseases like sickle cells. We explore many of these applications in our article “From Blindness to Meat Substitutes: CRISPR Gene-Editing Continues to Produce Promising Results”.
What makes CRISPR unique as a genetic tool is its capacity to match and identify exact genetic sequences precisely.
This accuracy is now being repurposed for testing diseases and might be simpler to use and more cost-efficient than the more common PCR tests.
Researchers from the Broad Institute, MIT, and Princeton University announced the release of a stripe test based on CRISPR technology, able to distinguish between the two main types of seasonal flu, influenza A and B, as well as seasonal flu subtypes H1N1 and H3N2.
Source: Broad Institute
How Does It Work?
The technology was first developed in 2020, under the name SHINE (Streamlined Highlighting of Infections to Navigate Epidemics). This was built on top of a previously developed CRISPR-based test method, SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing). While SHERLOCK was efficient, the multiple steps of the methods increased the risks of errors and erroneous readout.
Source: Nature
The new SHINE method can instead detect viruses with both a paper-based colorimetric readout and an in-tube fluorescent readout. Moreover, the fluorescent readout results can be interpreted in an automated fashion via a companion smartphone application.
Why It Matters
PCR testing is expensive and requires specialized equipment. As a result, only a small number of patients are tested (outside of pandemic conditions, of course), usually only the segment of patients visiting a hospital instead of their family doctor.
Antigen testing is often used as an alternative to PCR testing, but it is much less reliable and sensitive.
With correct strain identification with a low bar in terms of costs and complexity, clinicians could, for example, decide whether to use Oseltamivir. This common antiviral is effective for only some strains.
Another application would be helping scientists better monitor an epidemic outbreak through rapid testing in the field.
CRISPR Outperforming Previous Methods
The 2024 expansion of SHINE to different flu strains is aiming to replace the currently used method in pathology labs, especially PCR.
Typical diagnostic approaches such as polymerase chain reaction (PCR) require lengthy processing times, trained personnel, specialized equipment, and freezers to store reagents at -80°C, whereas SHINE can be conducted at room temperature in about 90 minutes. Currently, the assay only requires an inexpensive heat block to warm the reaction, and the researchers are working to streamline the process with the goal of returning results in 15 minutes.
Overall, CRISPR-based tests could perform better from a practical and commercial perspective and ultimately replace PCR when it comes to test highly variable viruses like flu and coronaviruses.
Next Viruses In Line
The upcoming version of the CRISPR-based strip tests will likely be expanded so that they can be used to detect the flu virus and which strain is present and distinguish between viruses with similar symptoms, like coronaviruses and influenza (flu virus).
Another urgent topic is the avian and swine influenza strains. These diseases are wreaking havoc on farming operations. They present serious risks to human health, even with a chance of causing a new pandemic if these viruses adapt from their animal hosts to humans.
Because of the previously demonstrated success with COVID and now flu, it is likely that CRISPR-based tests like SHINE will soon become a lot more common. This will be especially useful for quickly evolving viruses, where keeping track of different strains spread is crucial, a task in which antigen strips are usually performing poorly.
CRISPR Companies
1. Ginkgo Bioworks
The company is producing on-demand organisms for specific applications. These include biomedical applications and plenty of industrial and material sciences programs.
It also has a large biosecurity segment, which was booming during the pandemic.
Ginkgo Bioworks has diversified its applications widely with many research programs and partnerships:
It makes money by being first paid upfront for the development process and then through royalties on the finished product.
Gingko”s partnerships are constantly expanding, with:
Ginkgo Bioworks also partners with all the major agricultural corporations, most of which have some interests in biofuel production and microbiology. A few of these include Bayer, Cargill, Syngenta, Corteva, ADM, Exacta, and more.
Source: Gingko Bioworks
Gingko’s experience in custom designs of genetic sequences, as well as in biosecurity monitoring makes it a good candidate to benefit from the emergence of new DNA-based testing methods.
So with CRISPR-based tests now having been proven as a viable alternative to PCR tests (a massive market, even out of pandemic conditions), Gingko might be able to leverage its experience and partnership to grab a portion of this emerging market.
2. Editas Medicine, Inc.
Editas was founded by Jennifer Doudna, a discoverer of CRISPR-Cas9. Editas started working with Cas9 but is now focused on a proprietary version of Cas12 that they engineered: AsCas12a.
You can read more about Cas12a’s unique properties in our dedicated article “What Is CRISPR-Cas12a2? & Why Does It Matter?”.
To resume it shortly, Cas12as is unique because:
- Hard-to-solve problems with Cas9 could be workable with Cas12a
- This results in higher chances of gene editing than with Cas9.
- More than one gene can be modified at once with CAs12a.
You can also read an overview of all of Jennifer Doudna’s companies in the corresponding article “Top Jennifer Doudna Companies to Watch.”
Editas is focused on Sickle Cell Disease (SCD) and beta-thalassemia, 2 diseases where it lost the race for first treatment approval to competitors CRISPR Therapeutics and BlueBirdBio.
Nevertheless, Editas owns significant patents on CRISPR-Cas12, which has been used by other researchers at the University of New South Wales, Australia, to develop a COVID-19 strip test (the strip test from the Broad Institute researchers mentioned above used CRISPR-Cas13).
Editas focuses on other CRISPR versions than the “classical” CRISPR-Cas9 might come in handy in entering quickly the CRISPR strip test market and commercializing (with or without partnership) their own version of the strip tests developed by researchers in leading universities.