Methods for treating viral infections
AssigneePTC Therapeutics, Inc.
InventorsSergey V. Paushkin, Nikolai A. Naryshkin, Ellen Welch
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Abstract
The present invention relates to compounds that modulate ribosomal frameshifting and nucleic acid constructs for use in methods for identifying or validation such compounds. In particular, the present invention relates to the use of nucleic acid constructs to identify or validate compounds capable of modulating the efficiency of programmed ribosomal frameshifting and the use of said compounds to inhibit the replication or infectivity of viruses that employ programmed ribosomal frameshifting.
Claims27
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A nucleic acid construct comprising, in 5′ to 3′ order:
- (a) a start codon;
- (b) a minimum of one nucleotide;
- (c) a fragment of the nucleic acid residues of exon 7 of SMN, wherein the fragment of the nucleic acid residues of exon 7 of SMN comprises a minimum of the first six nucleotides from the 3′ end of exon 7 of SMN and wherein a single guanine residue is inserted into the fragment of the nucleic acid residues of exon 7 of SMN at the location that corresponds to the location in exon 7 of SMN that is after the 48th nucleotide from the 5′ end of exon 7 of SMN;
- (d) the nucleic acid residues of intron 7 of SMN or a fragment thereof, wherein the fragment of the nucleic acid residues of intron 7 of SMN comprises any number of nucleotides of intron 7 required for a functional, minimum intron;
- (e) a fragment of the nucleic acid residues of exon 8 of SMN;
- and (f) a reporter gene coding sequence lacking a start codon, wherein:
- (i) the reporter gene coding sequence is fused to the fragment of the nucleic acid residues of exon 8 of SMN such that the first codon of the reporter gene coding sequence and the first codon of the fragment are out of frame with each other in the mRNA transcript transcribed from the nucleic acid construct;
- and (ii) the production of the mRNA transcript generates a stop codon upstream from the reporter gene coding sequence in the region of the mRNA transcript that corresponds to the fragment of the nucleic acid residues of exon 8 of SMN;
- and (iii) the first start codon and the stop codon upstream from the reporter gene coding sequence in the mRNA transcript are in the same contiguous open reading frame without any interruption.
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Dependencies are inferred from the claim text.