The CRISPR Revolution
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a recently discovered tool for genetic editing. It allows for very precise and directed gene editing, and its discoverers have won the 2020 Nobel Prize.
Source: Lab Associates
The initial CRISPR system discovered was CRISPR-Cas9, and many modified CRISPR systems have been discovered or created since. You can read more about the technical details of CRISPR in our article “What Is CRISPR-Cas12a2? & Why Does It Matter?”
CRISPR is at the forefront of the genomic revolution, with the first gene therapies using it now getting approved for blood diseases, something we explored in depth in “How CRISPR Companies Target Sickle Cell Anemia”.
Almost every month that passes seems to bring a brand new revolutionary CRISPR therapy or application. The latest in date is curing a rare form of blindness.
Curing Blindness With CRISPR?
In a scientific paper titled “Gene Editing for CEP290-Associated Retinal Degeneration”, researchers and doctors at the Universities of Harvard Medical School, Pennsylvania, Michigan, Miami, Oregon Health and Science, as well as Perelman School of Medicine and Editas Medicine have seen remarkable results in treating a disease called Leber Congenital Amaurosis (LCA)
LCA causes the degradation of the vision in the first early months of life. There is currently no treatment for LCA, and affects an estimated 50,000 people in the USA and 180,000 people worldwide.
Source: Frontiers
After a break in 2022, Editas Medicine announced in May 2024 that the clinical trial for EDIT-101 has seen 79% of the 14 clinical trial participants experience measurable improvement after receiving the experimental gene therapy.
“One of our trial participants has shared several examples, including being able to find their phone after misplacing it and knowing that their coffee machine is working by seeing its small lights.
While these types of tasks might seem trivial to those who are normally sighted, such improvements can have a huge impact on quality of life for those with low vision.” – Mark Pennesi, M.D., Ph.D. – Oregon Health & Science University’s lead scientist
Next Steps For EDIT-101
Now that the efficiency of the treatment is proven, and there were no serious side effects, the next step is determining the “ ideal dosing, whether a treatment effect is more pronounced in certain age groups such as younger patients, and include refined endpoints to measure impacts on activities of daily living.”
“Our hope is that the study will pave the road for treatments of younger children with similar conditions and further improvements in vision.
This trial represents a landmark in the treatment of genetic disease, in specific genetic blindness, by offering important alternative treatment when traditional forms of therapy, such as gene augmentation, are not an option.” – Tomas S. Aleman, M.D. – Pediatric ophthalmologist at the Children’s Hospital of Philadelphia.
Most Recent CRISPR Progresses
The Coming Of In-Vivo CISPR
The results from EDIT-101 show the potential of the “in-vivo” approach to CRISPR therapies, which differs from the “ex-vivo” method used in the now-approved CRISPR therapies for blood diseases like sickle cell disease and beta-thalassemia.
(We discussed in detail this first-ever approved CRISPR treatment in our article “Sickle Cell Disease Gene Therapies Approved by FDA Highlighting Potential of CRISPR/Cas9 Technologies”).
A cure for congenital blindness might be only the beginning of such therapies, with other promising results:
- In January 2024, a world first was established in the successful treatment of an 11-year-old boy born with congenital deafness. The clinical trial was carried out by Eli Lilly(LLY) and a small biotechnology firm it owns, Akouos. Using CRISPR to cure deafness was explored in our article “Hearing Restored in Deaf Children in Gene Therapy Clinical Trial”.
- Excision Bio‘s EBT-101 therapy for human immunodeficiency virus (HIV) had its first positive trial results (safety profile), and is looking to start therapeutic evaluation, intending to “excise the integrated retrovirus from the genome of human cells”.
- Verve Therapeutics has two in-vivo gene therapies in the working, VERVE-101 and VERVE-102, both targeting cardiovascular diseases.
- The company”s technology relies on base editing, a potentially safer and/or more powerful option than classic CRISPR gene editing.
- Base editing is a topic we discussed before, in “Gene Editing: CRISPR Therapeutics vs. Beam Therapeutics”. And Beam Therapeutics, another champion of base editing, is progressing as well.
- Beam Therapeutics looks to use base editing to edit CAR-T cells to treat T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LL)
Others are working on leveraging CRISPR against cancer, including CRISPR Therapeutics, Ginkgo Bioworks Holdings, Editas Medicine., Caribou Biosciences, and Intellia Therapeutics. We explore this topic in further detail in our article “How Can CRISPR Be Used to Treat Cancer”.
CRISPR Beyond Medicine
If CRISPR is safe to modify patients’ bodies, it is also safe to change our food. For example, it could be used to create meat alternatives made from mushrooms that taste and feel like meat, as we saw in “Using CRISPR-Cas9 to Gene Hack Edible Mycelium Into Meat Substitutes.”
In “CRISPR Beyond Human Health: The New Investing Frontier for Gene Editing“, we explained how CRISPR will also be used to modify plants, achieving more controlled genetic modifications to create new crop varieties, reduce the need for pesticide and herbicides, or invent more efficient algal biofuels.
It will also be used to create more product livestock and maybe turn plants and animals into biofactories producing human medicine, ready-to-transplant organs, organic spices & fragrances, etc.
CRISPR could even be used to “resurrect” dead species, with the company Colossal Laboratories & Biosciences working on recreating a mammoth from frozen DNA, using CRISPR.
Leveraging New Technologies
More Data
A bit part of the edge of biotech innovation is the technological progress in other scientific fields.
A first boost to genetic science was the rise of cheap mass genome sequencing, as we saw when we examined the 2 largest sequencer manufacturers, in “Illumina vs Pacific Bioscience: Choosing the Next Generation Genome Sequencing Company”.
More precise analytical tools are also becoming mature, notably spatial biology (“Spatial Biology: Nanostring vs 10x Genomics“) and overall the convergence of many -omics like proteomics, transcriptomics, metabolomics, etc. into the multiomic analyses (“Multiomics Are The Next Step In Biotechnology”)
Managing Data With AI
For the longest period in medical history, getting good data on what is going on in the body was a difficult challenge.
The flood of new analytical tools has left medical sciences with an opposite problem: too much data to process and so complex they are almost impossible to understand. We explored this topic with many examples in our article “Advances in AI and CRISPR Technologies To Expedite Our Understanding of Genetic Diseases”.
AI tools like DeepCRISPR, CRISTA, and DeepHF are being used to guide RNAs for a specified target sequence. Predicting optimal guide RNAs takes multiple factors into account, such as genomic context, desired mutation type, on-target scores, off-target scores, prospective off-target locations, and the possible impacts of gene editing on its function.
AI models further help optimize different technologies to edit the genome, such as base (making targeted changes to the sequence of a piece of DNA), prime (a ‘search-and-replace’ editing), and epigenome (adding or removing molecular markers from DNA), which allows for precise and programmable changes to DNA sequences without relying on the donor DNA templates.
The best part is that such tools will not restricted to proprietary software, locked behind closed doors by the pharmaceutical industry.
Instead, new AI tools to optimize CRISPR gene editing are now released in an open-source format, as we talked about in “AI-Enabled Gene-Editing Made Possible with ‘OpenCRISPR-1’”.
CRISPR Companies
1. CRISPR Therapeutics
What sets CRISPR Therapeutics apart is the all-star team of founders, which includes Dr. Emmanuelle Charpentier whose seminal research unveiled the key mechanisms of the CRISPR-Cas9 technology, laying the foundation for the use of CRISPR-Cas9 as a versatile and precise gene-editing tool. Numerous awards have recognized her work, including the Breakthrough Prize in Life Science.
CRISPR Therapeutics is developing an efficient and versatile CRISPR/Cas9 gene-editing platform for therapies to treat hemoglobinopathies, cancer, diabetes, and other diseases.
The first therapy that they were advancing was targeting the blood diseases β-thalassemia and sickle cell disease.
They have now been approved under the commercial name of Casgevy and for both applications. The company’s first allogeneic CAR-T program targeting B-cell malignancies is also in clinical trials.
While sickle cell is a disease with an arguably small market, once the technology is mature they can advance to targeting other disease vectors.
As the first company with an approved CRISPR therapy, CRISPR Therapeutics is in a good position to be first to generate positive cash flow from the technology and expand its applications further.
And this stellar track record will likely make the company a partner of choice for any other pharmaceutical company looking to catch up in CRISPR therapies.
2. Ginkgo Bioworks Holdings, Inc.
The company is producing on-demand organisms for specific applications. It has widely diversified its applications with many research programs and partnerships:
Many of these modifications rely on CRISPR or similar gene editing technologies, notably its CAR-T cancer cell therapies.
By providing a ready platform for cell engineering, Ginkgo is becoming a key service provider in the biotech industry, going beyond the pharmaceutical industry and into agriculture, biosecurity, and industrial chemical processes. It provides expertise and speed and can help reduce fixed costs and the quantity of capex needed for a research project.
This is demonstrated by the very diverse array of clients and partners the company has had over the last few years.
Source: Gingko Bioworks
It is an attractive stock for investors looking to bet on gene editing and cell engineering technologies, but not one application in particular. This is also typically more interesting for growth-focused investors.
The large majority of CRISPR companies are focused on human medicine and genetic diseases, leaving open for Gingko opportunities in agriculture, bioengineering, energy, and bio-products (including cannabinoids). Together with the quick expansion of genetic datasets, gene editing tools, and AI (including open source), this could prove a massive opportunity for Gingko Bioworks.