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Novel Method for Finding Low Abundance Sequences By Hybridization

This invention describes a novel method for enriching rare sequences in nucleic acid libraries.

SEQUENCING OF NUCLEIC ACIDS VIA BARCODING IN DISCRETE ENTITIES

This invention identifies a method to prepare nucleic acid barcodes using microfluidic methods; allowing for high throughput analysis of many individual samples.

PCR-Activated Sorting (PAS)

This invention identifies a novel method for nucleic acid sorting, whether free-floating or contained in structures (eg. cells and viruses) using droplet microfluidics and PCR.

Targeted biological signal enhancement

This research tool consists of a two-vector system that can recruit an amplified biological signal to intra-cellular targets of interest.

Novel Method of Using Modified and Optimized Bacterial-derived Genetic CRISPR System for Imaging, Regulating and Editing Mammalian Genomic Elements

This invention is a novel method using optimized small guide RNAs (sgRNAs) to enable dynamic imaging, editing and regulation of specific genomic elements in living mammalian cells via the CRISPR system.

Acat-2, A Second Mammalian Acyl Coa:Cholesterol Acyltransferase That Is Involved In Cholesterol Metabolism

Acyl-COA: cholesterol acyl transferases or ACAT is an enzyme that catalyzes the esterification of cholesterol to form cholesteryl ester. Minimally, ACAT-mediated formation of cholesteryl ester from cholesterol prevents the toxic accumulation of excess cholesterol in a cell and maintains a free diffusion gradient across the cell membrane, particularly in the small intestine. In addition, the assembly and secretion of Apolipoprotein-B containing lipoproteins in the liver and intestines is thought to be dependent on the ACAT-mediated formation of cholesteryl esters from cholesterol. In steroidogenic tissue such as the adrenal glands, ACAT activity produces cytosolic droplets loaded with cholesteryl esters from which they can be mobilized as cholesterol substrates for the generations of steroids. Furthermore, macrophages that accumulate cholesteryl ester in cytosolic lipid droplets as a result of ACAT activity appear foamy and are a characteristic early indicator of atherosclerotic lesions. Animal models that completely lack ACAT protein are viable, albeit with tissue-specific reductions in cholesteryl ester, suggesting that another ACAT enzyme is present in these animals.

Targeted Intracellular Delivery of Nucleic Acids via Conjugation to Non-Lipid Carrier Molecules

Use of synthetic nucleic acids to manipulate gene function has become a powerful tool for both basic research and therapeutics.  Silencing disease targets by RNA interference is a promising approach to drug development, and various experimental RNA therapies are currently in clinical development by both small and large biotechnology companies.  miRNAs are also being developed for disease treatment and diagnosis.  However, lack of specifically targeted, efficient and safe vehicles for systemic delivery of small RNA payloads in vivo is a serious challenge.  Synthetic nucleic acids face a number of physiological barriers in the bloodstream, and their intracellular uptake is hampered by the fact that they are highly charged and have much larger molecular wieght than small-molecule drugs.  Current strategies to circumvent these problems includes local administration, chemical modifications of nucleic acids, viral delivery vectors, lipid-based delivery systems, polymer-based delivery systems and nanoparticle encapsulation.  These methods have serious flaws including toxicity, inummue effects, non-selectively and high cost of manufacturing.  Therefore, novel ways to deliver synthetic nucleic acids for use in humans and experimental animal models are sorely needed.

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