Abstract:
An assay for screening test compounds to indentify agents which modulate the binding of an E6-BP polypeptide with a papilloma virus E6 protein. The assay includes combining, as a cell-free system, an E6-binding protein or fragment thereof which binds to the E6 protein, and a test compound, and detecting the formation of a complex which includes the E6 protein and the E6-binding protein. A change in the formation of the complex in the presence of the test compound is indicative of an agent that modulates interaction between an E6 and an E6-binding protein.
Abstract:
The present invention is directed to methods and compositions capable of blocking the inhibitory effect of a newly-identified intronic inhibitory sequence element, named ISS-N1 (for “intronic splicing silencer”), located in the SMN2 gene. The compositions and methods of the instant invention include oligonucleotide reagents (e.g., oligoribonucleotides) that effectively target the SMN2 ISS-N1 site in the SMN2 pre-mRNA, thereby modulating the splicing of SMN2 pre-mRNA to include exon 7 in the processed transcript. The ISS-N1 blocking agents of the invention cause elevated expression of SMN protein, thus compensating for the loss of SMN protein expression commonly observed in subjects with spinal muscular atrophy (SMA).