The emergence of CRISPR technology, which can be used for gene modification and editing, has been revolutionary for the science community and research field due to its applications for disease and health. Additionally, combining nanotechnology and CRISPR can hold tremendous potential for widening the opportunities for versatile applications, from diseases to agriculture.
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What is CRISPR?
CRISPR is an acronym for ‘clustered regularly interspaced short palindromic repeats’ and is a critical tool that can be used to find specific DNA within cells for the purpose of gene editing; this can also include turning a gene ‘on’ or ‘off’ without modifying the sequence.
Conventional gene therapy methods have taken researchers years to gain traction and can be quite expensive; however, the emergence of CRISPR has revolutionized this process into a cheaper and relatively simpler strategy for gene editing.
CRISPR Cas9 proteins found in bacteria can be programmed to find and bind to targeted DNA sequences by providing a complimentary piece of RNA, which can guide the tool for its purpose. Once found, the Cas9 protein can cut the target DNA, which during repair, can lead to mutations and the disablement and overall dysfunction of the gene.
Other types of applications for CRISPR can also include replacing dysfunctional genes, turning genes on and off, instead of modifying the DNA, and even modifying single nucleotide bases within the DNA sequence from one letter to another. However, these can have varying levels of difficulties in practice.
Challenges
CRISPR/Cas9 delivery can be used for innovative cancer therapy; however, this would require the gene-editing tool to be delivered directly into target cancer cells, requiring the passing of physical barriers and maintaining functionality.
The strategies for delivery of the CRISPR system can include physical and viral vectors.
The physical vectors can include (i) microinjection, (ii) electroporation, and (iii) hydrodynamic delivery. These delivery methods have demonstrated efficiency within in vitro application; however, in vivo results have been more challenging.
Viral vectors have also been subject to challenges within in vivo applications, with limitations comprising immunogenic responses, high production expense, limited capacity with cargo packaging, as well as having possible effects outside of the target area.
Research into non-viral vectors and the possible use of nanotechnology to advance delivery has been explored as a result.
Nanotechnology in CRISPR
Non-viral nanotechnology-based delivery methods may include the use of nanocarriers, such as polymers, lipids, silica nanoparticles and metallic nanoparticles.
These have been revered for various applications in different fields due to their versatility and have also been used within cancer therapy due to advantages such as having low immunogenicity and a high cargo delivery capacity.
The high potential of the CRISPR/Cas9 system within clinical applications has been recognized globally by researchers, evident from 18 CRISPR-based clinical trials that have been launched since 2016, with almost half being a type of immunotherapy.
Additionally, the use of nanotechnology for furthering this gene-editing tool for diverse applications such as cancer, HPV treatment, as well as agriculture may advance the field of science and healthcare on a global scale.
A previous clinical trial has demonstrated the use of CRISPR/Cas9 on the human papillomavirus (HPV) that is associated with cervical cancer, where the correlated genes, E6 and E7, were destroyed to inhibit cancer cell proliferation and overall survival.
However, while trials have shown effective results, human safety remains a priority, with off-target effects and delivery being a concern for the CRISPR/Cas9 system.
The use of a lipid nanoparticle-based CRISPR/Cas9 system has recently been applied to treat transthyretin amyloidosis (ATTR), becoming the first clinical data of therapeutic gene editing within patients. This nanotechnology incorporation into CRISPR gene editing has demonstrated the potential of using nanotechnology to advance the treatment of genetic disorders through innovative delivery.
Future Outlook
With the global CRISPR market being valued at $846.2 million in 2019 and estimations of $10,825.1 million by the year 2030, at a compound annual growth rate of 26.86%, this gene-editing tool is predicted to have a significant impact worldwide.
The potential of editing the genome to modify human disease and disorders may be a tangible reality in the near future, with clinical trials already launched and set in motion.
Additionally, the use of nanotechnology for this advanced gene-editing tool may aid in satisfying concerns over have off-target effects due to the precise targetability characteristic for which this innovative field is known.
The versatility of nanotechnology enables the possibility of aiding the field of medicine as well as other fields, such as agriculture. This is critical as CRISPR systems also face delivery challenges within plants and with the use of nanomaterials, these may be solved.
With the growth of the global population, the essential survival of plants has become even more imperative to sustain the global demand for food, therapeutics, and bioenergy.
Genetic engineering methods are not only significant for medicine, but also for one of the most critical elements of life, namely, plants, to ensure species survival, higher yield, and nutrient density.
Nanotechnology uses for interdisciplinary applications have become a common theme and the opportunities for advancing the lives and health of humans are a critical component for research. The use of nanotechnology-based CRISPR can only advance the field further, providing promising solutions for current challenges.
References and Further Reading
Demirer, G., Silva, T., Jackson, C., Thomas, J., W. Ehrhardt, D., Rhee, S., Mortimer, J. and Landry, M., 2021. Nanotechnology to advance CRISPR–Cas genetic engineering of plants. Nature Nanotechnology, 16(3), pp.243-250. Available at: https://doi.org/10.1038/s41565-021-00854-y
Markets, R., 2022. Outlook on the CRISPR Gene Editing Global Market to 2030 - Analysis and Forecasts. [online] GlobeNewswire News Room. Available at: https://www.globenewswire.com/news-release/2021/02/08/2171285/0/en/Outlook-on-the-CRISPR-Gene-Editing-Global-Market-to-2030-Analysis-and-Forecasts.html
New Scientist. 2022. CRISPR. [online] Available at: https://www.newscientist.com/definition/what-is-crispr/
Uddin, F., Rudin, C. and Sen, T., 2020. CRISPR Gene Therapy: Applications, Limitations, and Implications for the Future. Frontiers in Oncology, 10. Available at: 10.3389/fonc.2020.01387
Xu, X., Liu, C., Wang, Y., Koivisto, O., Zhou, J., Shu, Y. and Zhang, H., 2021. Nanotechnology-based delivery of CRISPR/Cas9 for cancer treatment. Advanced Drug Delivery Reviews, 176, p.113891. Available at: https://doi.org/10.1016/j.addr.2021.113891
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