CRISPR Technology – An Emerging Solution in Healthcare

CRISPR technology has been gaining growing acceptance and popularity in the healthcare sector. Its varied applications in medical science has fostered innovations, with many startups entering the fray. However, CRISPR is a complex concept, and the technology is still at the nascent stage of development. Many new applications are under trials and await approval for launch. Moreover, the technology is marred with some underlying ethical issues. A strong regulatory framework will ensure the appropriate use of CRISPR.

CRISPR is an acronym for Clustered, Regularly Interspaced, Short Palindromic Repeats. Also known as the CRISPR-Cas9 system, it is a genome editing technology developed from a bacterial adaptive immune system. It revises, removes, and replaces target DNA. CRISPR is a dynamic and versatile technology that facilitates editing of nearly any location in the genome, and has the potential to help develop a cure for a wide variety of diseases.

The CRISPR-Cas9 system comprises a Cas9 endonuclease that can be programmed to target the genomic locus of interest with just a short guide RNA (sgRNA). The system has potential to cure disease-related genes or modify cells.

In 2021, the global CRISPR technology market was estimated to be valued at approximately USD2,251 million. The market is forecast to expand at a CAGR of 19% over 2022–27 to reach USD6,453 million by 2027. Major market drivers are:

• Increasing interest and investments by government and private investors
• Demand and adoption in various fields
• Technological advancements

The technology is also making waves in biotechnology and agriculture industries.

That said, healthcare applications have helped CRISPR grow into a niche segment.

CRISPR Applications in Healthcare

• Gene Editing – The CRISPR-Cas 9 system introduced a new era in biological science by allowing scientists to make target genetic sequence changes. The right combination of nuclease and guide RNA can help achieve high levels of specificity. The SpCas-9 system is preferred in gene editing applications. This system fuels continual search for different types of Cas proteins from other archaeal and bacterial species. The results have been positive, with an increasing number of variants differing in altered protospacer adjacent motif (PAM) requirements, target nucleic acid (DNA/RNA), nature of cutting, size, etc., being reported. Cas proteins are categorized into two classes, with six types and 33 subtypes. Only a few variants have potential gene editing applications. Specific characteristics of the following Cas proteins render them particularly attractive for gene editing applications.
  • Cas 12 – Makes a staggered cut in dsDNA
  • Cas 13 – Targets RNA
  • Cas 14 – Targets ssDNA
  • SaCas 9 – Compact size enables in-vivo gene editing
• Creating Cell and Animal Models – CRISPR genome editing has aided the rapid progress in research of a cure for fatal diseases, including cancer and mental illness. It allows scientists to quickly create cell and animal models and conduct genome-wide screening to map essential genes in a biological process.
• Multiplex Genome Editing – Though in nascent stages, the use of CRISPR in combination with other elements like non-pathogenic virus has shown promising results in treating neurodegenerative diseases. Merging CRISPR-Cas9 with multiple guide RNAs will enable single-step editing of several genes.
• Xenotransplantation – The technique has been plagued with ethical and moral issues. Despite this, xenotransplantation or creating human organs in animals is a potential lifesaver for patients on an ever-growing organ transplant list. CRISPR/Cas9 gene editing technology can help create organs with required immune and regulatory profiles, as evidenced by the creation of genetically modified pigs with human organs.
• Modulating Antibiotics – In the past decade, CRISPR technology has proved to be a potent antimicrobial modality, owing to its programmable sequence-specific nature. This can not only remove specific bacteria or virulence traits from the population but also leave the microbiota intact, a characteristic that antibiotics lack. CRISPR antimicrobials have proved to be lethal to microbes when injected via different biological carriers, such as phages and plasmids, and directed to the chromosome. These can also eliminate plasmids harboring antibiotic-resistant genes and sensitize bacteria to antibiotics.
• Diagnostics – CRISPR systems are varied. Currently, six types and 22 subtypes have been discovered and explored. Among these, types II, V, and VI find use in diagnostics. Illnesses from virus or bacteria and critical diseases, such as cancer, can be diagnosed using CRISPR enzymes. Researchers have already designed diagnostic tests using Cas12 and Cas13 enzymes to detect the SARS-CoV-2 virus. In addition, CRISPR diagnostic tests can reduce lab and patient costs, as these can be performed using simple reagents and paper-based lateral flow assays.

Through gene editing, scientists have discovered a new method to produce complex antibiotics. The technique can be used to combat antimicrobial resistance, treat neglected diseases, and prevent pandemics. CRISPR-cas9 gene editing is being used to create new non-ribosomal peptide synthetase (NRPS) enzymes that deliver clinically important antibiotics. Until now, it has been difficult to manipulate complex enzymes to make new antibiotics. They are prolific producers of natural antibiotics, such as penicillin.

Emerging Innovative Players in the Market

The CRISPR technology ecosystem has attracted an influx of startups. It has encouraged innovations across industries, while startups are contributing phenomenally. A few startups that entered the ecosystem are described below.

• NTrans – Founded in 2015 by Marco De Boer, NTrans developed a proprietary platform technology for the intercellular delivery of bioactive molecules. It pioneered a cellular uptake mechanism, which aids in delivering CRISPR components for therapeutic purposes. The startup is working on genome engineering to ensure the platform’s compatibility with all cell types.
• Mammoth Biosciences – Jennifer Doudna, Janice Chen, Lukas Harrington, and Trevor Martin founded Mammoth Biosciences in 2017. The company created a multi-analyte diagnostic platform and developed a SARs-CoV-2 detection platform.
• eGenesis – George Church and Luhan Yang founded eGenesis in 2014. The company focuses on CRISPR-based xenotransplantation. It aims to develop safe xeno (pig) organs for transplantation in humans.
• Caribou Biosciences – Founded in 2011 by Jennifer A. Doudna, James Berger, Rachel E. Haurwitz and Martin Jinek, Caribou Biosciences is using CRISPR genome editing technology to develop novel therapeutic candidates to treat patients with intractable malignancies.
• CRISPR Therapeutics – In 2014, Rodger Novak, Emmanuelle Charpentier, and Shaun Patrick Foy founded CRISPR Therapeutics. The company focuses on designing gene therapies for hereditary disorders, such as thalassemia.

CRISPR-based Clinical Therapies

Significant advances have been made recently in CRISPR-based therapeutics.

• Regeneron and Intellia Therapeutics’ NTLA-2001 gene therapy candidate for hereditary transthyretin amyloidosis is undergoing phase I trials.
• Editas Medicine’s gene-edited cell therapy EDIT-301 received IND clearance from FDA for phase I/II trials.
• Excision BioTherapeutics received IND clearance from FDA for initiating phase I/II trials for their CRISPR-based HIV treatment.

Outlook

While CRISPR technology is being rapidly adopted, ethical issues hinder its use, which must be addressed. Ensuring compassionate use of this technology will call for: (a) addressing issues of accessibility and cost; (b) appropriate and impartial review of clinical trials; and (c) stringent regulatory policies.

Despite developmental and ethical challenges, the technology has a bright future ahead. CRISPR is a scientific breakthrough that can prove to be a cure for diseases, such as cancer and infectious disorders. Researchers will have to devise simple yet effective ways to track its efficacy. CRISPR also has potential applications in therapeutic treatments, and thus, revolutionize this space. Though in nascent stages, CRISPR’s varied features will aid in addressing many healthcare issues.