Nucleic acid ligands and uses therefor
OwnerPeter Stockley, Christopher Adams +4inventors
InventorsPeter Stockley, Christopher Adams, David Bunka, Roma Rambaran, Simon Phillips, Sheena Radford
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Abstract
The present invention relates to novel nucleic acid molecules or ligands or aptamers with affinities for specific target molecules, and uses of such molecules. The target molecules are fibrillar proteins in all forms of the protein that is to say its monomeric, pre-fibrillar, protofibrillar and mature fibrillar forms. The molecules of the present invention are therefore useful as diagnostic or therapeutic or screening agents, or as potential lead compounds for ralionalised drug design.
Claims34
A purified and isolated non-naturally occurring nucleic acid ligand to a fibrillar protein target, wherein said ligand is an RNA ligand selected from the group consisting of:
- (i) the nucleic acid depicted in any one of SEQ ID NOS:
- 1-55 or 58-105;
- (ii) having the corresponding DNA or RNA sequences of any one of SEQ ID NOS:
- 1-55 or 58-105 or the corresponding fully complementary sequences thereof or their L-ribose derivatives;
- and
- (iii) derivatives of the sequence depicted in any one of SEQ ID NOS:
- 1-55 or 58-105 having at least about 60%, 70%, 80% or 90% sequence identity to any one of the nucleotide sequences, and which have a binding affinity to a fibrillar protein.
Use of a binding motif comprising a peptide sequence derived from human β2m that retains the ability of the whole protein to form amyloid fibrils, as a target for selecting a nucleic acid ligand.
Use of a peptide sequence comprising any one of SEQ ID NO:
- 111, 112 or 113 or derivatives or variants thereof that retain the ability of the whole protein to form amyloid fibrils, as a target for selecting a nucleic acid ligand.
A purified and isolated non-naturally occurring nucleic acid ligand to a fibril cross β-core protein target.
A method for the isolation of nucleic acid ligands to a fibrillar protein target comprising:
- (i) preparing a candidate mixture of nucleic acids;
- (ii) contacting the candidate mixture of nucleic acids with a biotinylated immobilised fibrillar protein on ice, wherein nucleic acids having an increased affinity to the fibrillar protein relative to the candidate mixture are partitioned from the remainder of the candidate mixture;
- (iii) partitioning the increased-affinity nucleic acids from the remainder of the candidate mixture;
- (iv) amplifying the increased-affinity nucleic acids to yield a mixture of nucleic acids with relatively high affinity and specificity for binding to the fibrillar protein, whereby a nucleic acid ligand of the fibrillar protein may be identified.
Dependencies are inferred from the claim text.