Tyrosyl-DNA Phosphodiesterases (TDP) and Related Polypeptides, Nucleic Acids, Vectors, TDP-Producing Host Cell, Antibodies and Methods of Use

Topisomerases are cellular enzymes that are vital for replication of the genome. However, if topisomerase and DNA form covalent complexes that prevent the resealing of DNA, this may lead to cell death. Essentially, this invention consists of a new isolated and cloned enzyme, tyrosyl-DNA phospodiesterase (TDP1) that is capable of hydrolyzing the covalent complexes between topisomerase and DNA, allowing the DNA to reseal.

Chromatin Insulator Protecting Expressed Genes of Interest for Human Gene Therapy or Other Mammalian Transgenic Systems

The technology provides the isolation of a functional DNA sequence comprising a chromatin insulating element from a vertebrate system and provides the first employment of the pure insulator element as a functional insulator in mammalian cells. The technology further relates to a method for insulating the expression of a gene from the activity of cis-acting regulatory sequences in eukaryotic chromatin.

Method of Diagnosing Multidrug Resistant Tuberculosis

The invention can be used to develop tests that are much more rapid than conventional tests for determining drug resistance. It relates to the discovery that a putative gene of Mycobacterium tuberculosis (MTb) with no previously identified function is responsible for the ability of the bacteria to activate a class of second line thioamide drugs used for MTb infections. The gene, termed "etaA", codes for the synthesis of a monooxygenase, the enzyme responsible for the oxidative activation of the drugs.

Methods for Diagnosis of Atherosclerosis

The identification of more sensitive and specific markers of atherosclerosis that are non-invasive and cost-effective may have profound impacts on public health. One such strategy involves the detection of marker genes or their products in blood or serum. Such markers may help identify high-risk patients with subclinical atherosclerosis who may benefit from intensive primary prevention or they may help determine the activity of established disease for monitoring response to treatment, resulting in more targeted secondary prevention.

Farnesyltransferase Inhibitors for Treatment of Laminopathies, Cellular Aging and Atherosclerosis

Hutchinson-Gilford Progeria Syndrome (HGPS) is a very rare progressive childhood disorder characterized by premature aging (progeria). Recently, the gene responsible for HGPS was identified (Eriksson M, et al. Nature 2003), and HGPS joined a group of syndromes — the laminopathies — all of which are caused by various mutations in the lamin A/C gene (LMNA). Lamin A is one of the family of proteins that is modified post-translationally by the addition of a farnesyl group.

Tristetraprolin (TTP) Knockout Mice

National Institutes of Health researchers have developed knockout mice that do not express Tristetraprolin (TTP). TTP is an AU-rich element (ARE) binding protein and the prototype of a family of CCCH zinc finger proteins. AREs were identified as conserved sequences found in the 3’ untranslated region (3’ UTR) of a variety of transiently expressed genes including early response genes, proto-oncogenes, and other growth regulatory genes. AREs function as instability sequences that target ARE-containing transcripts for rapid mRNA decay.

AAV4 Vector and Uses Thereof

The invention described and claimed in this patent application relates to the delivery of heterologous nucleic acids or genes to particular target cells. In particular, the application relates to methods of delivering a heterologous nucleic acid or gene of interest to particular target cells using Adeno-Associated Virus of serotype 4 (AAV4). The particular target cells identified are the ependymal cells of the brain. The methods described herein may be useful in carrying out gene therapy for diseases of the brain or central nervous system.

TTP as a Regulator of GM-CSF mRNA Deadenylation and Stability

The disclosed invention provides materials and methods to treat granulocytopenia (low white cell count in the blood) which is characterized by a reduced number of granulocytes (relative) or an absence of granulocytes (absolute). This condition is commonly associated with cancer chemotherapy, but is seen less frequently in a number of conditions including the use of propylthiouracil, radiotherapy for marrow ablation for bone marrow transplantation, aplastic anemia, systemic lupus erythematosus, AIDS and a variety of other situations.

AAV5 Vector for Transducing Brain Cells and Lung Cells

The invention described and claimed in this patent application is related to the delivery of heterologous nucleic acids or genes to particular target cells. In particular, the application relates to methods of delivering a heterologous nucleic acid or gene of interest to particular target cells using an Adeno-Associated Virus of serotype 5 (AAV5). The particular target cells identified include the alveolar cells of the lung and cerebellar and ependymal cells of the brain.