Transcytosis of Adeno-Associated Viruses

The invention relates to a method for delivering nucleic acids to a variety of cells including those of the gut, kidney, lung and central nervous system. The underlying cells of such organs are covered by a barrier of endothelial or epithelial cells which can limit the transfer of nucleic acids, or other potentially therapeutic agents, to the underlying target cells. To overcome this limitation, the method employs certain members of the parvovirus family to transcytose the barrier cells.

Construction of Recombinant Baculoviruses Carrying the Gene Encoding the Major Capsid Protein, VP1, From Calicivirus Strains (Including Norovirus Strains Toronto, Hawaii, Desert Shield, Snow Mountain, and MD145-12)

The noroviruses (known as "Norwalk-like viruses") are associated with an estimated 23,000,000 cases of acute gastroenteritis in the United States each year. Norovirus illness often occurs in outbreaks, affecting large numbers of individuals, illustrated recently by well-publicized reports of gastroenteritis outbreaks on several recreational cruise ships and in settings such as hospitals and schools.

Construction of an Infectious Full-Length cDNA Clone of the Porcine Enteric Calicivirus RNA Genome

Porcine enteric calicivirus (PEC) is a member of the genus Sapovirus in the family Caliciviridae. This virus causes diarrheal illness in pigs, and is presently the only enteric calicivirus that can be grown in cell culture. In addition to its relevance to veterinary medicine as a diarrheal agent in pigs, PEC serves as an important model for the study of enteric caliciviruses that cause diarrhea and that cannot be grown in cell culture (including the noroviruses represented by Norwalk virus).

Enzymatically-Active RNA-Dependent RNA Polymerase From a Human Norovirus (Calicivirus)

The noroviruses (formerly known as “Norwalk-like viruses”) are associated with gastroenteritis outbreaks, affecting large numbers of individuals each year. Emerging data are supporting their increasing recognition as important agents of diarrhea-related morbidity and mortality. The frequency with which noroviruses are associated with gastroenteritis as “food and water-borne pathogens” has led to the inclusion of caliciviruses as Category B Bioterrorism Agents/Diseases.

Full-Length cDNA Clone Representing the Consensus Sequence of the RNA Genome of a Human Norovirus (strain MD145-12) That Encodes Biologically Active Proteins

The invention provides for a full-length cloned cDNA copy of the RNA genome of a predominant norovirus strain (Genogroup II.4) designated MD145-12 that was associated with human gastrointestinal illness. The noroviruses, which were formerly known as "Norwalk-like" viruses are estimated to cause 23 million cases of acute gastroenteritis in the USA each year. The virus has been designated into category B of the CDC biodefense-related priority pathogens because it can be used as an agent of bioterrorism.

Cloning and Characterization of an Avian Adeno-Associated Virus and Uses Thereof

Currently, adeno-associated virus (AAV) represents the gene therapy vehicle of choice because it has many advantages over current strategies for therapeutic gene insertion. AAV is less pathogenic than other virus types; stably integrates into dividing and non-dividing cells; integrates at a consistent site in the host genome; and shows good specificity towards various cell types for targeted gene delivery.

Regulation of RNA Stability

This invention relates to the discovery that tristetraprolin (TTP) can promote the poly(A)RNase (PARN) mediated deadenylation of polyadenylated substrates containing AU-rich elements (AREs). As one aspect of the invention, the inventors have developed a cell free system that may be used for the purposes of assessing the effects of the various system components or their derivatives (i.e. AREs, PARN, or TTP) on the deadenylation process or the effects of various test agents on the deadenylation process.

Peptide Mimotope Candidates for Otitis Media Vaccine

This technology describes peptide mimotopes of lipooligosaccharides (LOS) from nontypeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis that are suitable for developing novel vaccines against the respective pathogens, for which there are currently no licensed vaccines. The mimotopes not only immunologically mimic LOSs from NTHi and M. catarrhalis but will also bind to antibodies specific for the respective LOS. NTHi and M. catarrhalis are common pathogens that cause otitis media in children and lower respiratory tract infections in adults.

Variable Curve Catheter

The invention provides a deflectable tip guiding device, such as a catheter, that enables the operator to vary the radius of curvature of the tip of the catheter. This is a novel variation on the classic "fixed fulcrum" tip deflectors used in minimally invasive procedures in open surgical treatments. The described device permits a more comprehensive ability to navigate complex geometric pathways in patient's body and enables better access to target structures (e.g., to all endomyocardial walls from a transaortic approach).

Tryptophan as a Functional Replacement for ADP-ribose-arginine in Recombinant Proteins

Bacterial toxins such as cholera toxin and diphtheria toxin catalyze the ADP-ribosylation of important cellular target proteins in their human hosts, thereby, as in the case of cholera toxin, irreversibly activating adenylyl cyclase. In this reaction, the toxin transfers the ADP-ribose moiety of Nicotinamide Adenine Dinucleotide (NAD) to an acceptor amino acid in a protein or peptide. ADP-ribosylation leads to a peptide/protein with altered biochemical or pharmacological properties. Mammalians proteins catalyze reactions similar to the bacterial toxins.