SEMMs: Somatically Engineered Mouse Models. A New Tool for In Vivo Disease Modeling for Basic and Translational Research
Most experimental oncology therapies fail during clinical development despite years of preclinical testing rationalizing their use. This begs the question of whether the current preclinical models used for evaluating oncology therapies adequately capture patient heterogeneity and response to therapy...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-04-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.667189/full |
| _version_ | 1818741306334117888 |
|---|---|
| author | Anthony Lima Danilo Maddalo Danilo Maddalo |
| author_facet | Anthony Lima Danilo Maddalo Danilo Maddalo |
| author_sort | Anthony Lima |
| collection | DOAJ |
| description | Most experimental oncology therapies fail during clinical development despite years of preclinical testing rationalizing their use. This begs the question of whether the current preclinical models used for evaluating oncology therapies adequately capture patient heterogeneity and response to therapy. Most of the preclinical work is based on xenograft models where tumor mis-location and the lack of the immune system represent a major limitation for the translatability of many observations from preclinical models to patients. Genetically engineered mouse models (GEMMs) hold great potential to recapitulate more accurately disease models but their cost and complexity have stymied their widespread adoption in discovery, early or late drug screening programs. Recent advancements in genome editing technology made possible by the discovery and development of the CRISPR/Cas9 system has opened the opportunity of generating disease-relevant animal models by direct mutation of somatic cell genomes in an organ or tissue compartment of interest. The advent of CRISPR/Cas9 has not only aided in the production of conventional GEMMs but has also enabled the bypassing of the construction of these costly strains. In this review, we describe the Somatically Engineered Mouse Models (SEMMs) as a new category of models where a specific oncogenic signature is introduced in somatic cells of an intended organ in a post-natal animal. In addition, SEMMs represent a novel platform to perform in vivo functional genomics studies, here defined as DIVoS (Direct In Vivo Screening). |
| first_indexed | 2024-12-18T01:54:32Z |
| format | Article |
| id | doaj.art-894cbf64024742ca87f542a9f83254d7 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-18T01:54:32Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-894cbf64024742ca87f542a9f83254d72022-12-21T21:24:57ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-04-011110.3389/fonc.2021.667189667189SEMMs: Somatically Engineered Mouse Models. A New Tool for In Vivo Disease Modeling for Basic and Translational ResearchAnthony Lima0Danilo Maddalo1Danilo Maddalo2Department of Translational Oncology, Genentech, Inc., South San Francisco, CA, United StatesDepartment of Translational Oncology, Genentech, Inc., South San Francisco, CA, United StatesRoche Pharmaceuticals, Basel, SwitzerlandMost experimental oncology therapies fail during clinical development despite years of preclinical testing rationalizing their use. This begs the question of whether the current preclinical models used for evaluating oncology therapies adequately capture patient heterogeneity and response to therapy. Most of the preclinical work is based on xenograft models where tumor mis-location and the lack of the immune system represent a major limitation for the translatability of many observations from preclinical models to patients. Genetically engineered mouse models (GEMMs) hold great potential to recapitulate more accurately disease models but their cost and complexity have stymied their widespread adoption in discovery, early or late drug screening programs. Recent advancements in genome editing technology made possible by the discovery and development of the CRISPR/Cas9 system has opened the opportunity of generating disease-relevant animal models by direct mutation of somatic cell genomes in an organ or tissue compartment of interest. The advent of CRISPR/Cas9 has not only aided in the production of conventional GEMMs but has also enabled the bypassing of the construction of these costly strains. In this review, we describe the Somatically Engineered Mouse Models (SEMMs) as a new category of models where a specific oncogenic signature is introduced in somatic cells of an intended organ in a post-natal animal. In addition, SEMMs represent a novel platform to perform in vivo functional genomics studies, here defined as DIVoS (Direct In Vivo Screening).https://www.frontiersin.org/articles/10.3389/fonc.2021.667189/fullclustered regularly interspaced short palindromic repeat/CRISPR associated protein 9-mediated genome editingmouse modelsgenetically engineered mouse modelssomatically engineered mouse modelstranslational researchanimal models |
| spellingShingle | Anthony Lima Danilo Maddalo Danilo Maddalo SEMMs: Somatically Engineered Mouse Models. A New Tool for In Vivo Disease Modeling for Basic and Translational Research Frontiers in Oncology clustered regularly interspaced short palindromic repeat/CRISPR associated protein 9-mediated genome editing mouse models genetically engineered mouse models somatically engineered mouse models translational research animal models |
| title | SEMMs: Somatically Engineered Mouse Models. A New Tool for In Vivo Disease Modeling for Basic and Translational Research |
| title_full | SEMMs: Somatically Engineered Mouse Models. A New Tool for In Vivo Disease Modeling for Basic and Translational Research |
| title_fullStr | SEMMs: Somatically Engineered Mouse Models. A New Tool for In Vivo Disease Modeling for Basic and Translational Research |
| title_full_unstemmed | SEMMs: Somatically Engineered Mouse Models. A New Tool for In Vivo Disease Modeling for Basic and Translational Research |
| title_short | SEMMs: Somatically Engineered Mouse Models. A New Tool for In Vivo Disease Modeling for Basic and Translational Research |
| title_sort | semms somatically engineered mouse models a new tool for in vivo disease modeling for basic and translational research |
| topic | clustered regularly interspaced short palindromic repeat/CRISPR associated protein 9-mediated genome editing mouse models genetically engineered mouse models somatically engineered mouse models translational research animal models |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.667189/full |
| work_keys_str_mv | AT anthonylima semmssomaticallyengineeredmousemodelsanewtoolforinvivodiseasemodelingforbasicandtranslationalresearch AT danilomaddalo semmssomaticallyengineeredmousemodelsanewtoolforinvivodiseasemodelingforbasicandtranslationalresearch AT danilomaddalo semmssomaticallyengineeredmousemodelsanewtoolforinvivodiseasemodelingforbasicandtranslationalresearch |