Lipid Nanoparticles Deliver the Therapeutic VEGFA mRNA In Vitro and In Vivo and Transform Extracellular Vesicles for Their Functional Extensions.

Lipid nanoparticles (LNPs) are currently used to transport functional mRNAs, such as COVID-19 mRNA vaccines. The delivery of angiogenic molecules, such as therapeutic VEGF-A mRNA, to ischemic tissues for producing new blood vessels is an emerging strategy for the treatment of cardiovascular diseases. Here, the authors deliver VEGF-A mRNA via LNPs and study stoichiometric quantification of their uptake kinetics and how the transport of exogenous LNP-mRNAs between cells is functionally extended by cells' own vehicles called extracellular vesicles (EVs).

Development of an ObLiGaRe Doxycycline Inducible Cas9 system for pre-clinical cancer drug discovery.

The CRISPR-Cas9 system has increased the speed and precision of genetic editing in cells and animals. However, model generation for drug development is still expensive and time-consuming, demanding more target flexibility and faster turnaround times with high reproducibility. The generation of a tightly controlled ObLiGaRe doxycycline inducible SpCas9 (ODInCas9) transgene and its use in targeted ObLiGaRe results in functional integration into both human and mouse cells culminating in the generation of the ODInCas9 mouse.

Variable flip angle 3D ultrashort echo time (UTE) T mapping of mouse lung: A repeatability assessment.

Background: Lung T is a potential translational biomarker of lung disease. The precision and repeatability of variable flip angle (VFA) T mapping using modern 3D ultrashort echo time (UTE) imaging of the whole lung needs to be established before it can be used to assess response to disease and therapy.

Purpose: To evaluate the feasibility of regional lung T quantification with VFA 3D-UTE and to investigate long- and short-term T repeatability in the lungs of naive mice.

In vivo imaging of lipid storage and regression in diet-induced obesity during nutrition manipulation.

Changes in adipose tissue distribution and ectopic fat storage in, liver and skeletal muscle tissue impact whole body insulin sensitivity in both humans and experimental animals. Numerous mouse models of obesity, insulin resistance, and diabetes exist; however, current methods to assess mouse phenotypes commonly involve direct harvesting of the tissues of interest, precluding the possibility of repeated measurements in the same animal. In this study, we demonstrate that whole body 3-D imaging of body fat composition can be used to analyze distribution as well as redistribution of fat after intervention by repeated assessment of intrahepatocellular lipids (IHCL), intra-abdominal, subcutaneous, and total adipose tissue (IAT, SAT, and TAT) and brown adipose tissue (BAT).

Automatic segmentation of intra-abdominal and subcutaneous adipose tissue in 3D whole mouse MRI.

Purpose: To fully automate intra-abdominal (IAT) and total adipose tissue (TAT) segmentation in mice to replace tedious and subjective manual segmentation.

Materials And Methods: A novel transform codes each voxel with the radius of the narrowest passage on the widest possible three-dimensional (3D) path to any voxel in the target object to select appropriate IAT seed points. Then competitive region growing is performed on a distance transform of the fat mask such that competing classes meet at narrow passages effectively segmenting the IAT and subcutaneous adipose compartments.