Genetics INSIGHTS

RNA-based therapeutics are a relatively new class of drugs based on RNA sequences. There are three main classes of RNA therapeutics: small interfering RNA (siRNA), RNA aptamers, and ribozymes. siRNA Therapeutics and Gene Expression Last year, the first siRNA-based therapeutic was approved by the FDA. The drug, called ONPATTRO® (patisiran), developed by Alnylam Pharmaceuticals, aims to treat peripheral nerve disease caused by hereditary transthyretin-mediated (hATTR) amyloidosis in...  Read More

Genetically modified mice and rats have been around for decades. But, until recently, the cost and effort involved in generating genetically engineered models (GEMs) using the available technologies were relatively high. This meant that requesting access to a model described in the literature was the fastest way to start a research project with that reagent, even if the material transfer agreement (MTA) or license process delayed transfer...  Read More

Single nucleotide polymorphisms (SNPs) are variations in the genome that occur when a single nucleotide is altered. While single base-pair changes may seem minor, they are key indicators of strain differences among mice and rats1. SNP testing is vital in many colony management applications, from background verification and genetic screening to creating a mouse model on a different background through the speed congenic process. How SNP Testing...  Read More

An article published recently in Science highlights the unique journey of two identical twins — Mark and Scott Kelly — who have enabled the study of extended space flight and the effects it has on the human body. Together, they spent a combined 574 days in space. Both are retired US Navy Captains and astronauts. Since identical twins share the same genetic makeup, studying the changes that...  Read More

Maintaining genetic integrity within breeding colonies is always a critical issue, but this is especially the case for germ-free and gnotobiotic mice1. Due to the small size and closed nature of most gnotobiotic colonies, these lines are especially vulnerable to genetic drift via the accumulation of novel mutations2,3. In the worst-case scenario, this might lead to the unintentional fixation of mutations in inbred strains, with potentially devastating...  Read More

Reproducibility Requires Genetic Quality The genetic integrity of laboratory mice and rats is an important contributor to research reproducibility, which is why commercial animal vendors invest in maintaining the genetic quality of standard inbred and outbred strains. As the technology to produce genetically engineered models (GEMs) becomes more widespread, a growing majority of GEMs are bred and used at individual institutions. This decentralization has created concerns regarding...  Read More

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...  Read More

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...  Read More

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...  Read More

The Sprague Dawley® (SD) rat is one of the most popular outbred stocks, with application across many therapeutic areas as well as ADMET studies. The SD is an outbred stock, meaning that there is genetic variation within the stock, and each individual varies in genetic makeup. Genetic variation is maintained through well-defined rotational mating schemes, which are designed to maintain heterozygosity within the population over time. The...  Read More