Harnessing the potential of gene editing and patient-derived organoids in human therapeutics
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The field of organoids can benefit from CRISPR-Cas9 technology, which has revolutionised genome editing is now applicable to the organoids research as well. The ground-breaking study by Schwank and colleagues showed that human genetic diseases can be corrected in patient-derived organoids using CRISPR-Cas9-based gene editing. Then, using organoids and animal models, researchers have used this technique to simulate and treat a variety of human ailments.
Before gene editing may be used to cure disease in humans, many obstacles must be overcome. Patients' access to direct gene editing is now restricted by challenges with vector delivery, HDR's low efficiency, and the possibility of unwanted insertions, deletions, and off-target consequences. It is possible to choose, screen for, and grow clones with the required mutations by editing patient-derived cells or organoids.
Combining organoids with this gene editing method [CRISPR/Cas9] is a potentially fruitful strategy for studying other human tumors
- Johns Hopkins Medicine researchers claim they have developed a laboratory-grown three-dimensional "organoid" model that is derived from human tissue and intended to advance understanding about how early stages of cancer develop at the GEJ.
- The scientists subsequently eliminated two important tumour suppressor genes (TP53 and CDKN2A) using the gene editing technique clustered regularly interspaced palindromic repeats (CRISPR/Cas9) in the organoids. These genes were both knocked out, which increased the cancerousness of the cells and gave them faster development and microscopic characteristics indicative of malignancy. These modified organoids also produced tumours in immunocompromised mice.
- The team further found abnormalities in a class of molecules (lipids) that store energy but also exert a variety of other functions, and identified platelet-activating factor as a key upregulated lipid in GEJ organoids. Platelets circulate in the bloodstream and bind together or clot when they recognize damaged blood vessels, and they can cause clotting diseases in some people. Researchers used WEB2086, which stopped the growth of implanted GEJ organoid tumors. Before employing the substance on human patients, additional preclinical research may be necessary, however, the use of organoids may speed up these research processes.
Crown Bioscience inked a licensing deal with ERS Genomics to use its CRISPR/Cas9 patent portfolio for gene editing
- To exploit ERS Genomics' CRISPR/Cas9 patent portfolio for gene editing in the creation of novel therapies for cancer, immuno-oncology, and immune-mediated inflammatory illnesses, Crown Bioscience signed a licencing agreement with the company. According to a news release from Crown Bioscience on December 8, 2022, the partnership enables the company to increase its gene editing capabilities and advance the use of gene editing in 3D patient-derived tumour organoid models. The agreement also positions the JSR Life Sciences-owned preclinical services company in a position to get licences from "all applicable patent holders" and to use the technology to provide commercial services across the globe.
- CRISPR gene editing has great promise for improving and modifying cells, including potentially patient-derived organoids, in both 2D and 3D. CRISPR is being used ever more extensively to transform biotechnology. It's fantastic to utilise CRISPR to modify cells involved in the creation of organoids, and it's fascinating to see other CRISPR applications being explored.
BioIntel360 projects that gene modification in patient-derived organoids can be used right away in the clinic in near future to assess if alterations are harmful and to test treatments. However, reliable knock-in techniques are missing for the exact integration of exogenous DNA sequences into human organoids. In the future, cells from healed patients may be cultivated in sophisticated tissue scaffolds before being transplanted.