CRISPR somatic genome engineering and cancer modeling in the mouse pancreas and liver

Kaltenbacher, Thorsten; Löprich, Jessica; Maresch, Roman; Weber, Julia; Müller, Sebastian; Oellinger, Rupert; Groß, Nina; Griger, Joscha; Avramopoulos, Petros; Ramanujam, Deepak; Brummer, Sabine; Widholz, Sebastian A.; Bärthel, Stefanie; Falcomatà, Chiara; Fischer, Anja; Alnatsha, Ahmed; Mayerle, Julia; Schmidt-Supprian, Marc; Reichert, Maximilian; Schneider, Günter; Ehmer, Ursula; Braun, Christian; Saur, Dieter; Engelhardt, Stefan; Rad, Roland

doi:10.1038/s41596-021-00677-0

Cited by 16 publications

(4 citation statements)

References 133 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AAV9-hSyn-iCre was produced as outlined previously 78 . In brief, HEK293-T cells were seeded in 10-tray Cell Factories (Thermo Fisher Scientific) 24 hours before transfection, allowing the cells to reach 80-90 % confluence.…”

Section: Methodsmentioning

confidence: 99%

Polyglutamylation of microtubules drives neuronal remodeling

Gavoci,

Zhiti,

Rusková

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Developmental remodeling shapes neural circuits via activity-dependent pruning of synapses and axons. The cytoskeleton is critical for this process, as microtubule loss via enzymatic severing is an early step of pruning across many circuits and species. However, how microtubule-severing enzymes, such as spastin, are activated in specific neuronal compartments remains unknown. Here, we reveal that polyglutamylation, a posttranslational tubulin modification that is enriched in neurons, plays an instructive role in developmental remodeling by tagging microtubules for severing. Motor neuron-specific gene deletion of enzymes that add or remove tubulin polyglutamylation—TTLL glutamylases vs. CCP deglutamylases—accelerates or delays neuromuscular synapse remodeling in a neurotransmission-dependent manner. This mechanism is not specific to peripheral synapses but also operates in central circuits, e.g., the hippocampus. Thus, tubulin polyglutamylation acts as an activity-dependent rheostat of remodeling and shapes neuronal morphology and connectivity.

show abstract

Section: Methodsmentioning

confidence: 99%

Polyglutamylation of microtubules drives neuronal remodeling

Gavoci,

Zhiti,

Rusková

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…On the other hand, the incomplete penetrance of mutations in GEMMs leads to delayed cancer onset, causing nonsynchronous tumor occurrence among mice 344 . The development of nongermline GEMMs, conditional GEMMs, and advancements in genome editing technologies like CRISPR‐Cas9 have helped overcome these limitations 29,335,345 . As an illustration, when delivering potent tumor suppressors ( Tp53 and Cdkn2a ) targeted sgRNAs and Cas in GEMM liver, tumor formations were only observed when additional triggers existed, including Kras G12D mutation and CCl 4 related inflammation 346 …”

Section: In Vivo Mouse Model For Tumor Immunology Investigationmentioning

confidence: 99%

Biomarkers and experimental models for cancer immunology investigation

Xu,

Jia,

Liu

et al. 2023

MedComm

View full text Add to dashboard Cite

The rapid advancement of tumor immunotherapies poses challenges for the tools used in cancer immunology research, highlighting the need for highly effective biomarkers and reproducible experimental models. Current immunotherapy biomarkers encompass surface protein markers such as PD‐L1, genetic features such as microsatellite instability, tumor‐infiltrating lymphocytes, and biomarkers in liquid biopsy such as circulating tumor DNAs. Experimental models, ranging from 3D in vitro cultures (spheroids, submerged models, air–liquid interface models, organ‐on‐a‐chips) to advanced 3D bioprinting techniques, have emerged as valuable platforms for cancer immunology investigations and immunotherapy biomarker research. By preserving native immune components or coculturing with exogenous immune cells, these models replicate the tumor microenvironment in vitro. Animal models like syngeneic models, genetically engineered models, and patient‐derived xenografts provide opportunities to study in vivo tumor‐immune interactions. Humanized animal models further enable the simulation of the human‐specific tumor microenvironment. Here, we provide a comprehensive overview of the advantages, limitations, and prospects of different biomarkers and experimental models, specifically focusing on the role of biomarkers in predicting immunotherapy outcomes and the ability of experimental models to replicate the tumor microenvironment. By integrating cutting‐edge biomarkers and experimental models, this review serves as a valuable resource for accessing the forefront of cancer immunology investigation.

show abstract

“…The chimeric antigen receptor T (CAR T) cells, expressed by CAR-expressing T cells, can specifically recognize and activate tumor cells as well as stimulate specific immune response of tumor cells to achieve tumor elimination immunotherapy [104] . PD-1 is involved in both activated and regulatory T cells, and in multiple tumor cells can be found its ligand, PD-L1 [105] , [106] , [107] .…”

Section: Application Of Crispr/cas9 In Hcc Therapymentioning

confidence: 99%