Low adenosine anti-sense oligonucleotide agent , composition , kit and treatments

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Jonathan W. Nyce (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: A composition comprises a nucleic acid comprising an oligo anti-sense to a target such as polypeptide(s) associated with an ailment afflicting lung airways , genes and mRNAs encoding them , genomic and mRNA flanking regions , intron and exon borders and all regulatory and functionally related segments of the genes and mRNAs encoding the polypeptides , their salts and mixtures. Various formulations contain a requisite carrier , and optionally other additives and biologically active agents. The agent of the invention may be prepared by selecting a target gene(s) , genomic flanking region(s) , RNA(s) and/or polypeptide(s) associated with a disease(s) or condition(s) afflicting lung airways , obtaining the sequence of the mRNA(s) corresponding to the target gene(s) and/or genomic flanking region(s) , and/or RNAs encoding the target polypeptide(s) , selecting at least one segment of the mRNA which may be up to 60 % free of thymidine (T) and synthesizing one or more anti-sense oligonucleotide(s) to the mRNA segments which are free of adenosine (A) by substituting a universal base for A when present in the oligonucleotide. The agent may be prepared by selection of target nucleic acid sequences with GC running stretches , which have low T content , and by optionally replacing A in the anti-sense oligonucleotides with a AUniversal base@. The agent , composition and formulations are used for prophylactic , preventive and therapeutic treatment of ailments associated with impaired respiration , allergy(ies) and/or inflammation , such as pulmonary vasoconstriction , inflammation , allergies , asthma , impeded respiration , lung pain , cystic fibrosis , bronchoconstriction , pulmonary hypertension and bronchoconstriction , chronic bronchitis , emphysema , chronic obstructive pulmonary disease (COPD) , acute respiratory distress syndrome (ARDS) , ischemic conditions including ischemia itself , and cancers such as leukemias , lymphomas , carcinomas , and the like , e.g. colon cancer , breast cancer , pancreatic cancer , lung cancer , hepatocellular carcinoma , kidney cancer , melanoma , hepatic metastasis , etc. , as well as all types of cancers with may metastasize or have metastasized to the lung(s) , including breast and prostate cancer. The present treatment is suitable for administration in combination with other treatments , e.g. before , during and after other treatments , including radiation , chemotherapy , antibody therapy and surgery , among others. The present agent is effectively administered preventatively , prophylactically or therapeutically by itself for conditions without known therapies , or as a substitute for , or in conjunction with , other therapies exhibiting undesirable side effects. The treatment of this invention may be administered directly into the respiratory system of a subject , so that the agent has direct access to the airways and the lungs.

Additional Information

Publication

Other

Language: English

Date: 2000

Keywords

DNA, Nucleotides, mRNA, Lung

Subjects

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