Myocardial hypertrophy and apoptosis are the underlying degenerative process associated with cardiac hypertrophy and failure. Substrate RNA and the specific RNA cleavage products generated by ribozyme cleavage are visualized on an autoradiograph ofthe gel. The rate of entry of a drug into the circulation has been shown to be a function of molecular weight or size. Such modified groups are described, for example, in Eckstein et al. By “inhibit” it is meant that the activity of target genes or level of mRNAs or equivalent RNAs encoding target genes is reduced below that observed in the absence of the nucleic acid molecules of the instant invention e. The molecule shown is only exemplary. Receptor tyrosine kinases propagate signal transduction events via extracellular receptor-ligand interactions that result in the activation ofthe tyrosine kinase portion ofthe PTK in the cytoplasmic domain.
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The sequences of the chemically synthesized ribozymes used in this study are shown below in Tables Figure 36 summarizes the results of functional group modification studies in which various nucleoside analogs were tested for activity in the NCH ribozyme motif.
Henderson, European Patent Application No. The method of synthesis used followed the procedure for normal RNA synthesis as described above and in Usman et al. The target sequences and the nucleotide location within the phospholamban RNA are given in Tables In addition, several in vitro selection evolution strategies Orgel,Proc.
These ribozymes can be tested for cleavage activity in vitro, for example using the following procedure. After attachment, fusion ofthe viral envelope and host membrane must occur to allow the viral core proteins containing the genome and polymerase to enter the cell.
HBV is transmitted via infected blood or other body fluids, especially saliva and semen, during delivery, sexual activity, or sharing of needles contaminated by infected blood.
In another embodiment, the expression vector iacm LekanneDeprez et al,J. For combination therapy, the nucleic acids ofthe invention are prepared in one of two ways. Antibodies are commercially available for HBV surface antigen and core protein. Telomerase was first discovered by in Tetrahymena thermophila in Greider, C.
An “alkyl” group refers to a saturated aliphatic hydrocarbon, including straight- chain, branched-chain, and cyclic alkyl groups. Various methods have been developed to assay phospholamban activity in vitro and in vivo.
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In preferred embodiments, the enzymatic nucleic acid inhibitors comprise ciam, which are complementary to the subsfrate sequences in Tables33, 34,56, 58, 59, 62, Rhesus monkeys were dosed with BrdU-labeled ribozyme by intravenous bolus injection at 0.
Since hTR expression does not correlate well with telomerase activity in human cells and since many human cells express hTR without telomerase activity, targeting hTERT may prove more beneficial than targeting icaam. Additional conserved telomere elements icaam a terminal 3 ‘-overhang in the G-rich strand and non-histone structural proteins that are complexed with telomeric DNA in the nucleus.
Alzheimer’s disease AD is a progressive, degenerative disease ofthe brain which affects approximately 4 million people in the United States alone. The support is washed three times with 1. For example, pharmacological compositions injected into the blood stream should be soluble.
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Wang et al,Proc. Individuals may be “carriers” and transmit the infection to others without ever having experienced symptoms ofthe disease. More preferably it is a lower alkynyl of from 1 to 7 carbons, more preferably 1 to 4 carbons. A variety of animal models have been designed to assay telomerase activity in vivo. Ribozymes and antisense constructs were designed to anneal to various sites in the RNA message.
The length ofthe binding dc4-130 s are preferably greater than or equal to four nucleotides and of sufficient length to stably interact with the target RNA; specifically nucleotides; more specifically 24 nucleotides long.
A percent complementarity indicates the percentage of contiguous residues in a nucleic acid molecule which can form hydrogen bonds e. A iczm effective dose is that dose required to prevent, inhibit the occurrence, or treat alleviate a symptom to some extent, preferably all ofthe symptoms of a disease state. More preferably it is a lower alkenyl of from 1 to 7 carbons, more preferably 1 to 4 carbons.
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Alternatively, viral vectors may be used that provide for transient expression of ribozymes or antisense. Ln the later stages of cirrhosis, patients are classified as decompensated meaning that their ability to detoxify metabolites in the bloodstream is diminished and it is at this stage that the clinical features.
Such liposomes have been shown to accumulate selectively in tumors, presumably by extravasation and capture in the neovascularized target tissues Lasic et al, Science, ; Oku et al.
This antigen is the dc-130 and most useful diagnostic marker for active infections. In particular embodiments, the nucleic acid molecule is,,,, or nucleotides in length.