GEMs Design INSIGHTS


Genetic Variation in C57BL/6 ES Cells and Knockout Mice

Genetically engineered animal models (GEMs) are powerful tools for biomedical research and drug discovery, but genetic variation in animal models derived from distinct ES cell lines and subsequent breeding can impact both the interpretation and reproducibility of studies which employ them1. While recent advances in gene editing accelerated the migration of models to a pure C57BL/6 background, researchers should remain aware of potentially confounding results from genetic...

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Cystic Fibrosis Treatment from Vertex May Restore Lung Function

Cystic Fibrosis (CF) is a genetic disorder that affects the lungs, digestive system, and a host of metabolic functions. In humans, CF is a progressive disease, where chronic dysfunction of muco-ciliary clearance leads to severe congestion, thick mucus build-up, and severe persistent lung infections. In 1960 the median life expectancy for a patient with CF was ten years old. However, with significant advances in research and clinical...

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Oh Transgene, Where Art Thou?
Mapping Transgene Insertion

Over the last three decades, transgenic mice have become a critical in vivo modeling tool in biomedical research. Transgenic technique1, whereby an exogenous gene is inserted into the mouse genome by direct injection of DNA into the pronuclei of a zygote, has enabled thousands of new transgenic lines to be created2. However the technique is not without limitations. One of the biggest drawbacks of using pronuclear injection...

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New Vici Syndrome Mouse Model Could Accelerate Research

Most rare diseases have a genetic component, making access to an animal model with the associated gene mutation a must for developing new therapies. Yet these diseases don't often attract the funding to develop a genetically engineered model of the condition. With the help of Taconic Biosciences, two investigators studying Vici syndrome now have this essential research tool in hand. Vici syndrome is a severe congenital multisystem...

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CRISPR Genome Engineering: Advantages and Limitations

Four years after the debut of CRISPR/Cas9 in mouse genetics, it is time to start drawing some conclusions on its performance, advantages, and limitations as a genome engineering technology1,2,3. Advantages of CRISPR Genome Engineering Arguably, the most important advantages of CRISPR/Cas9 over other genome editing technologies is its simplicity and efficiency. Since it can be applied directly in embryo, CRISPR/Cas9 reduces the time required to modify target...

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Why Your Transgenic Project Failed

Erroneous modification of the mouse genome can lead to the generation of transgenic lines carrying non-functional alleles or unwanted mutations. These faulty models can seriously impact your research program, wasting resources on misleading results. Are Design Errors Driving Translational Failure? Genetically modified mouse models first appeared more than thirty years ago and are still at the heart of biomedical research. The first models carried relatively simple genetic...

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Genetically Engineered Models in Drug Development

Why do 90% of compounds fail the FDA approval process after entering Phase I clinical trials?1 Many failed projects can be traced to unreliable preclinical assessments of toxicity and efficacy of the potential new drugs2 – often due to a lack of predictive and reliable in vivo testing. Wild-type mice and rats were the gold standard in the assessment of efficacy and toxicity for many years, due...

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Improving Lives by Modeling Rare Genetic Disorders

Relief for patients with rare genetic disorders are often out of reach, due to the expense of developing genetically engineered animal models. That's why the Rare Genomics Institute, Taconic Biosciences, and Jonah's Just Begun came together to develop and characterize a model of Sanfilippo Syndrome. Sanfilippo Syndrome is a progressive, devastating rare genetic disorder affecting approximately 1 in 70,000 children. There are four subtypes of the disease,...

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Modeling Proprioception

NPR recently published "How A 'Sixth Sense' Helps Simone Biles Fly, And The Rest Of Us Walk", that explored proprioception - the sense of the relative position of neighboring parts of the body - with a story on children with a rare mutation in a gene called PIEZO2. When Damiana was younger, her condition baffled doctors, says her mother, Diana Sawyer. "She was very late at doing...

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Biotechnology Patents and Genetically Modified Organisms

How do biotechnology patents affect the generation, use and distribution of genetically modified organisms, such as knockout mice or transgenic animal models? What is a licensing agreement and what are the implications of licensing (or not licensing) methods and technologies used in biomedical research? Can you use the new model you recently obtained from a collaborator for your research program? In a nutshell, patents protect intellectual property...

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