Genetic engineering in organoids

Teriyapirom, Isaree; Batista-Rocha, Andreia S.; Koo, Bon–Kyoung

doi:10.1007/s00109-020-02029-z

Cited by 42 publications

(31 citation statements)

References 127 publications

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“…Successful multihit oncogenic transformation of normal-tissue-derived organoids to carcinoma has been achieved by introducing simultaneous or sequential oncogenic mutations into tissues such as breast, stomach, pancreas and colon ( 31 , 93 – 96 ). Although several limitations need to be addressed including heterogeneous growth rates of organoids and single-guide RNA coverage ( 97 ), cancer organoids could serve as a promising platform for CRISPR–Cas9-mediated genome editing and large-scale screens to improve the efficacy of cancer immunotherapy.…”

Section: Combination Of Pdtos With Multiomicsmentioning

confidence: 99%

Patient-Derived Tumor Organoids: New Progress and Opportunities to Facilitate Precision Cancer Immunotherapy

et al. 2022

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Cancer immunotherapy has revolutionized the field of cancer treatment in recent years. However, not all patients receiving cancer immunotherapy exhibit durable responses, and reliable, high-throughput testing platforms are urgently needed to guide personalized cancer immunotherapy. The ability of patient-derived tumor organoids to recapitulate pivotal features of original cancer tissues makes them useful as a preclinical model for cancer research and precision medicine. Nevertheless, many challenges exist in the translation of tumor organoid research to clinical decision making. Herein we discuss the applications of patient-derived tumor organoid models and the advances and potential of using complex immune-organoid systems as testing platforms to facilitate precision cancer immunotherapy. In addition, we highlight intriguing applications of tumor organoids with novel multi-omics in preclinical cancer research, highlighting genetic editing, proteomics, and liquid biopsy.

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Section: Combination Of Pdtos With Multiomicsmentioning

confidence: 99%

Patient-Derived Tumor Organoids: New Progress and Opportunities to Facilitate Precision Cancer Immunotherapy

et al. 2022

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“…For instance, Helicobacter pylori can be injected into stomach organoids to study the mechanisms of gastritis and the bacterial contribution to carcinogenesis (Salama et al, 2013). Patient-derived tissues or specific genetic mutations could be used to produce organoids for genetic or tumor disease modeling (Cristobal et al, 2017;Finnberg et al, 2017;Cruz and Freedman, 2018;Berkers et al, 2019;Kampmann, 2020;Teriyapirom et al, 2021). The combination of the CRISPR-Cas9 system and organoid technology would constitute a successful approach to investigate the underlying mechanisms and signaling pathways of genetic and cancer diseases through gene mutation, fusion and repair (Hendriks et al, 2020).…”

Section: Development and Disease Modelingmentioning

confidence: 99%

To Better Generate Organoids, What Can We Learn From Teratomas?

Gao

et al. 2021

Front. Cell Dev. Biol.

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The genomic profile of animal models is not completely matched with the genomic profile of humans, and 2D cultures do not represent the cellular heterogeneity and tissue architecture found in tissues of their origin. Derived from 3D culture systems, organoids establish a crucial bridge between 2D cell cultures and in vivo animal models. Organoids have wide and promising applications in developmental research, disease modeling, drug screening, precision therapy, and regenerative medicine. However, current organoids represent only single or partial components of a tissue, which lack blood vessels, native microenvironment, communication with near tissues, and a continuous dorsal-ventral axis within 3D culture systems. Although efforts have been made to solve these problems, unfortunately, there is no ideal method. Teratoma, which has been frequently studied in pathological conditions, was recently discovered as a new in vivo model for developmental studies. In contrast to organoids, teratomas have vascularized 3D structures and regions of complex tissue-like organization. Studies have demonstrated that teratomas can be used to mimic multilineage human development, enrich specific somatic progenitor/stem cells, and even generate brain organoids. These results provide unique opportunities to promote our understanding of the vascularization and maturation of organoids. In this review, we first summarize the basic characteristics, applications, and limitations of both organoids and teratomas and further discuss the possibility that in vivo teratoma systems can be used to promote the vascularization and maturation of organoids within an in vitro 3D culture system.

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“…The extremely large packaging capacities of gutless Ad chassis make them ideally suited to carry Cas proteins, multiple gRNAs, and one or more transgene sequences. Platform technologies such as organoids, multiorgan-on-a-chip platforms, and spatial transcriptomics are granting a better understanding of how polygenic changes can influence cell, tissue, organ, and whole-organism physiology. While the experiments necessary to understand the multiscale effects of polygenic gene editing can produce massive amounts of data, artificial intelligence (AI) methodologies are well-poised to extract useful insights from such large data sets. , By putting together gutless Ad vectors equipped with multiplexed CRISPR-Cas systems with platforms which decipher physiological responses to polygenic changes, polygenic gene therapy may gain feasibility in the near future.…”

Section: Outlook On the Futurementioning

confidence: 99%

Synthetic Biology Approaches for Engineering Next-Generation Adenoviral Gene Therapies

Collins

Curiel

2021

ACS Nano

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Synthetic biology centers on the design and modular assembly of biological parts so as to construct artificial biological systems. Over the past decade, synthetic biology has blossomed into a highly productive field, yielding advances in diverse areas such as neuroscience, cell-based therapies, and chemical manufacturing. Similarly, the field of gene therapy has made enormous strides both in proof-of-concept studies and in the clinical setting. One viral vector of increasing interest for gene therapy is the adenovirus (Ad). A major part of the Ad's increasing momentum comes from synthetic biology approaches to Ad engineering. Convergence of gene therapy and synthetic biology has enhanced Ad vectors by mitigating Ad toxicity in vivo, providing precise Ad tropisms, and incorporating genetic circuits to make smart therapies which adapt to environmental stimuli. Synthetic biology engineering of Ad vectors may lead to superior gene delivery and editing platforms which could find applications in a wide range of therapeutic contexts.

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Genetic engineering in organoids

Cited by 42 publications

References 127 publications

Patient-Derived Tumor Organoids: New Progress and Opportunities to Facilitate Precision Cancer Immunotherapy

Patient-Derived Tumor Organoids: New Progress and Opportunities to Facilitate Precision Cancer Immunotherapy

To Better Generate Organoids, What Can We Learn From Teratomas?

Synthetic Biology Approaches for Engineering Next-Generation Adenoviral Gene Therapies

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