Modified plant virus particles and uses therefor
AssigneesPlant Bioscience Limited, Aura Biosciences, Inc.
InventorsGeorge Lomonossoff, David Evans, Elisabet de los Pinos, Frank Sainsbury
Life of this patent
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Abstract
Aspects of the invention provide modified virus-like particles that are designed for therapeutic applications. In particular, aspects of the invention provide CCMV coat proteins that are modified to generate virus-like particles, including mosaic virus-like particles, that can package and/or deliver one or more diagnostic and/or therapeutic agents. The invention also provides methods for treating subjects with one or more modified virus-like particles.
Claims24
1-91. (canceled)
A virus-like particle (VLP) preparation comprising:
- (a) a mosaic VLP of two or more different CCMV coat proteins, wherein at least one of the coat proteins is modified to include a targeting peptide that comprises an integrin-binding motif, and wherein
- (i) at least one of the coat proteins has a N-terminal deletion within the first 26 amino acids and wherein the deletion is of 1 to 26 amino acids in length,
- (ii) at least one of the coat proteins comprises an amino acid sequence of a bacteriophage coat protein or functional portion thereof,
- (iii) at least one of the coat proteins comprises one or more amino acid substitutions within the first 26 N-terminal amino acids and/or the coat protein comprises one or more amino acid substitutions and/or amino acid deletions within amino acids 52-176 of the coat protein,
- (iv) at least one of the coat proteins comprises a moiety selected from the group consisting of polyethylene glycol (PEG), hyaluronic acid, a natural or synthetic polymer, a histidine tag, folic acid, a second targeting peptide not comprising an integrin-binding sequence, an antibody or functional fragment thereof, and a receptor ligand molecule,
- (v) at least one of the coat proteins comprises an amino acid sequence that interacts selectively with a nucleic acid motif that is present on a heterologous RNA molecule;
- (b) a heterologous RNA molecule, wherein the heterologous RNA molecule is a microRNA (miRNA), a short interfering RNA (siRNA), a double-stranded RNA (dsRNA), a short hairpin RNA (shRNA), RNAu, or an antisense RNA molecule;
- and
- (c) a therapeutic molecule, wherein the therapeutic molecule is a therapeutic agent, a diagnostic agent or an imaging agent present in the interior of the assembled mosaic VLP.
A pharmaceutical composition comprising:
- (a) a mosaic VLP of two or more different CCMV coat proteins, wherein at least one of the coat proteins is modified to include a targeting peptide that comprises an integrin-binding motif, and wherein
- (i) at least one of the coat proteins has a N-terminal deletion within the first 26 amino acids and the deletion is of 1 to 26 amino acids in length,
- (ii) at least one of the coat proteins comprises an amino acid sequence of a bacteriophage coat protein or functional portion thereof,
- (iii) at least one of the coat proteins comprises one or more amino acid substitutions within the first 26 N-terminal amino acids and/or the coat protein comprises one or more amino acid substitutions and/or amino acid deletions within amino acids 52-176 of the coat protein,
- (iv) at least one of the coat proteins comprises a moiety selected from the group consisting of polyethylene glycol (PEG), hyaluronic acid, a natural or synthetic polymer, a histidine tag, folic acid, a second targeting peptide not comprising an integrin-binding sequence, an antibody or functional fragment thereof, and a receptor ligand molecule,
- (v) at least one of the coat proteins comprises an amino acid sequence that interacts selectively with a nucleic acid motif that is present on a heterologous RNA molecule;
- (b) a heterologous RNA molecule, wherein the heterologous RNA molecule is a microRNA (miRNA), a short interfering RNA (siRNA), a double-stranded RNA (dsRNA), a short hairpin RNA (shRNA), RNAu, or an antisense RNA molecule;
- and
- (c) a therapeutic molecule, wherein the therapeutic molecule is a therapeutic agent, a diagnostic agent or an imaging agent present in the interior of the assembled mosaic VLP.
Dependencies are inferred from the claim text.