Figure 7 shows examples of chemically stabilized ribozyme motifs. The recombinant vectors are preferably DNA plasmids or viral vectors. Ribozyme expressing viral vectors could be constructed based on, but not limited to, adeno-associated virus, retrovirus, adenovirus, or alphavirus. An “alkylaryl” group refers to an alkyl group as described above covalently joined to an aryl group as described above. An estimated five million Americans are afflicted with congestive heart failure CHF , with , new cases diagnosed each year. Such bases are generally located at the 1′ position of a nucleotide sugar moiety. However, the expression of human telomerase RNA hTR does not correlate well with telomerase activity in mammalian cells.

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Diuretics are often used to reduce pulmonary edema and dyspnea in patients with fluid overload, and are usually used in conjunction with angiotensin converting enzyme ACE inhibitors for vasodilation.

Hepatology a textbook of liver disease, Second Edition Volume 1. These icsm can be tested for cleavage activity in vitro, for example using the following procedure. If you are inexperienced with updating Chicony device drivers manually, we highly recommend downloading the Chicony iCam DC Driver Utility. The molecules ofthe instant invention can be used as pharmaceutical agents.

WOA2 – Nucleic acid based modulators of gene expression – Google Patents

By “homology” is meant the nucleotide sequence of two or more nucleic acid molecules is partially or completely ica. A pharmaceutically 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. Whereby the above treatment strategies can all improve morbidity and mortality associated with cardiac disease, the only existing definitive approach to curing the diseased heart is replacement by transplant.

In view of such teachings, similar modifications can be used as described herein to modify the nucleic acid molecules ofthe instant invention. HH Rz, represents hammerhead ribozyme motif Usman et al,Curr. In a non-limiting example, small scale syntheses are conducted on a Applied Biosystems, Inc.


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The cell may be prokaryotic e.

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Typically, antisense molecules will be complementary to a target sequence along a single contiguous sequence ofthe antisense molecule. Varying binding arm lengths can be chosen to optimize activity. The sequences ofthe chemically synthesized ribozymes and antisense constructs used in this study are shown below in Table Single mismatches, or base-substitutions, near the site of cleavage can be chosen to completely eliminate catalytic activity of a ribozyme. By “triplex DNA” it is meant an oligonucleotide that can bind to a double-stranded DNA in a sequence-specific manner to form a triple-strand helix.

In another aspect ofthe invention, RNA molecules ofthe present invention are preferably expressed from transcription units see, for example, Couture et al,TIG. Distribution of antisense oligonucleotides was determined by probing with an anti-BrdU antibody and immunohistochemical staining.

Once inside, the genome is translocated to the nucleus where it is repaired and cyclized.

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Activation of telomerase expression in cells at or nearing senescence as a result of ddc-4130 age or premature aging could benefit conditions such as macular degeneration, skin ulceration, and rheumatoid arthritis. A similar study employing MetAP-2 inhibition could be used to study ribozyme based inhibition of MetAP-2 induced angiogenesis in vivo.

The vial is brought to r.

Thus, use ofthe term “comprising” indicates that the listed elements are required or mandatory, but that other elements are optional and may or may not be present. Delivery of nucleic acid molecule expressing vectors could be systemic, such as by intravenous or intra-muscular administration, by administration to target cells ex-planted from the patient followed by reinfroduction into the patient, or by any other means that would allow for introduction into the desired target cell for a review see Couture et al,TIG, 12, Figure 14 is a schematic diagram of HCV luciferase assay used to demonstrate efficacy of class I enzymatic nucleic acid molecule motif.


A secreted alkaline phosphatase expression plasmid can be used to normalize for differences in transfection efficiency and sample recovery. PTP-IB dephosphorylation of multiple phosphotyrosine residues ofthe insulin receptor proceeds sequentially and with specificity for the three tyrosine residues that are critical for receptor autoactivation Ramachandran, C,Biochemistry, 31, H refers to bases A, U, or C.

Table II outlines the amounts and the contact times ofthe reagents used in the synthesis cycle. Binding arms can be complementary to the specified substrate, to a portion ofthe indicated substrate, to the indicated substrate sequence and additional adjacent sequence, or a portion ofthe indicated sequence and additional adjacent sequence. Synthesis of nucleic acids greater than nucleotides in length is difficult using automated methods, and the therapeutic cost of such molecules is prohibitive.

The alkynyl group may be substituted or unsubstituted. Chang et al, US patent No. At various time points 30 min, 2h and 6 hmice were sacrificed and major tissues isolated and fixed.

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