Genetic Engineering in Organoids

Organoids are three-dimensional, miniaturized, and simplified versions of organs that replicate the architecture and functionality of their in vivo counterparts. This makes them powerful tools for biological research, disease modeling, and regenerative medicine. Genetic engineering within organoids has significantly expanded their utility by enabling precise manipulation of genes and cellular behavior. As techniques become more refined, the potential of genetically engineered organoids in translational research and personalized medicine continues to grow, promising breakthroughs in the understanding and treatment of complex diseases. These organoids further enhance this innovation by introducing specific genetic modifications, which allows scientists to:

Functional Studies: Analyze how specific genes contribute to organ development, function, and disease.
Drug Testing and Development: Evaluate the efficacy and safety of drugs in organ-like systems that include genetic variations found in humans.
Personalized Medicine: Tailor treatments to patients by testing drugs on organoids developed from their stem cells and modified to simulate genetic conditions.

Figure 1. Process for establishing genetic engineering organoids.

Creative Bioarray offers a comprehensive suite of organoid genetic engineering services tailored to meet the needs of researchers and biomedical companies. These services enable groundbreaking advancements in the development and application of organoid models, leveraging cutting-edge technologies and innovative methodologies. Our services include:

Gene-Overexpression in Organoids

Organoid model: cervical cancer organoids
Method: Lentivirus-mediated gene overexpression

Figure 2. Exogenous genes were overexpressed in HPV16+ cervical cancer organoids. ^[1]

Gene-Knockdown in Organoids

Organoid model: non-small cell lung cancer organoids
Method: Lentivirus-mediated shRNA interference

Figure 3. Glutamine synthetase (GS) was knocked down by lentivirus-mediated shRNA in non-small cell lung cancer organoids. ^[2]

Gene-Knockout in Organoids

Organoid model: mouse intestinal tumor organoids
Method: Lentivirus CRISPR-Cas9–mediated gene knockout

Figure 4. CRISPR-Cas9–mediated gene knockout in mouse intestinal tumor organoids. ^[3]

Service Highlights

Abundant organoid models: Our organoid library covers different disease types and provides a wide range of models for genetic modification.
Mature construction strategies: The establishment and identification of organoid lines can be completed within 4 to 8 weeks.
Providing a variety of downstream research services: The constructed organoid model can be utilized for proliferation assay, drug sensitivity tests, apoptosis analysis, cell cycle analysis, in vivo animal experiments, tumor immunity assessments, and other functional tests and phenotype studies.
Supporting multi-omics approaches: The genetically modified organoid model can leverage various omics tools, including genome, transcriptome, proteome, and epigenetics, to facilitate mechanism research.

References

Xiong, Chengjie et al. "Identification of novel HLA-A*11:01-restricted HPV16 E6/E7 epitopes and T-cell receptors for HPV-related cancer immunotherapy." Journal for immunotherapy of cancer vol. 10,9 (2022): e004790. doi:10.1136/jitc-2022-004790
Zhao, Jiang-Sha et al. "Glutamine synthetase licenses APC/C-mediated mitotic progression to drive cell growth." Nature metabolism vol. 4,2 (2022): 239-253. doi:10.1038/s42255-021-00524-2
Takeda, Haruna et al. "CRISPR-Cas9-mediated gene knockout in intestinal tumor organoids provides functional validation for colorectal cancer driver genes." Proceedings of the National Academy of Sciences of the United States of America vol. 116,31 (2019): 15635-15644. doi:10.1073/pnas.1904714116

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