Phosphodiester and phosphorothioate oligodeoxynucleotides (18 mers) were constructed antisense to sequences of the recently cloned murine and human IL-1 receptors. Murine antisense oligonucleotides inhibited IL-1-stimulated PGE2 synthesis by murine fibroblasts in culture in a time (days) and concentration-dependent (3 microM-30 microM) fashion. Murine sense oligonucleotide and an oligonucleotid...

Neuromuscular disorders such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy are neurodegenerative genetic diseases characterized primarily by muscle weakness and wasting. Until recently there were no effective therapies for these conditions, but antisense oligonucleotides, a new class of synthetic single stranded molecules of nucleic acids, have demonstrated promising experimental r...

Squamous cell carcinoma of the head and neck (SCCHN) is one of the most common malignancies worldwide, with low 5-year survival rates. Current strategies that block epidermal growth factor receptor (EGFR) have limited effects when administered as single agents. Targeting EGFR via intratumoral administration of phosphorothioate-modified antisense oligonucleotides has antitumor efficacy in xenogr...

Background: Malignant melanoma is a highly metastatic cutaneous cancer and typically refractory to chemotherapy. Deregulated apoptosis has been identified as a major cause of cancer drug resistance, and upregulated expression of the inhibitor of apoptosis protein melanom, an inhibitor of apoptosis (ML-IAP) is frequent in melanoma. Methods: Based on the conclusion that ML-IAP expression contribu...

The use of antisense oligonucleotides as therapeutic agents has generated considerable enthusiasm in the research and medical community. Antisense oligonucleotides as therapeutic agents were proposed as far back as in the 1970s when the antisense strategy was initially developed. Nonetheless, it has taken almost a quarter of a century for this potential to be realized. The principle of antisens...

Ras oncogenes owe their transforming properties to single point mutations in the sequence coding for the active site of the p21 protein. These mutations lead to changes in cellular proliferation and induce tumorigenic properties. Point mutations represent a well-defined target for antisense oligonucleotides that can specifically suppress the translation of the targeted mutant mRNA. We show that...

Antisense oligonucleotides have been considered as inhibitors of growth of intracellular parasites such as Leishmania, but only limited inhibition has been observed in vitro. We have encapsulated an antisense oligonucleotide, complementary to the Leishmania universal miniexon sequence, in cationic liposomes. Low concentrations (4 microM) of encapsulated oligonucleotides specifically reduced the...

Antisense oligonucleotides can vary significantly and unpredictably in their ability to inhibit protein synthesis. Libraries of chimeric oligonucleotides and RNase H were used to cleave and thereby locate sites on human multidrug resistance-1 RNA transcripts that are relatively accessible to oligonucleotide hybridization. In cell culture, antisense sequences designed to target these sites were ...

DNA of human papillomavirus type 18 is present in several human cancer cell lines that were derived from oral or cervical tumors, and it is known that several features of the transformed phenotype can be inhibited by expression of antisense RNA to human papillomavirus (HPV). The present study was performed to find out whether antisense oligonucleotides were also inhibitory. Synthetic oligonucle...