Disclosed herein are polypeptides for use in treating diseases associated with pathogenic genomic repeat sequences, such as neurological disorders. Also disclosed are nucleic acid molecules and vectors that encode such polypeptides. Therapeutic uses and methods for treating such diseases are also disclosed; in particular, therapeutic uses and methods comprising complementary pairs and combinations of therapeutic polypeptides, nucleic acids or vectors. Also disclosed is a method and associated peptides and nucleic acids for active, long-term delivery of therapeutic molecules to target cells in vivo or in vitro.

A method for ex vivo transduction of biomolecules from viruses, viral vectors or virus-like particles into target cells and microbubbles for use in this method. A quantity of viruses, viral vectors or virus-like particles and target cells are bound to flexible lipid shell microbubbles, bringing these into close proximity to each other that allows viral transduction, transferring biomolecules from the viruses, viral vectors or virus-like particles into the target cells while the viruses, viral vectors or virus-like particles and the target cells are bound to the microbubbles.

Disclosed herein are polypeptides for use in treating diseases. Therapeutic uses and methods for treating diseases are also disclosed. Also disclosed is a method and associated peptides and nucleic acids for active, long-term delivery of therapeutic molecules to target cells in vivo or in vitro.

The invention relates to a method for providing a virus-like particle (VLP) derived from John Cunningham virus (JCV), relates to a VLP associated with a cargo, in particular a protein, and a drug delivery system (DDS) obtainable by said method, in particular for crossing the blood brain barrier (BBB), and a VLP containing composition. The method comprises steps of disassembly of VLP into pentamers, inducing the pentamers to aggregate and reassembly into VLP.

The invention relates to VLP derived from human polyoma virus loaded with a drug (cargo) as a drug delivery system for transporting said drug into the CNS, in particular of living humans.

The invention relates to a method for providing a drug delivery system, in particular for crossing the blood brain barrier (BBB), comprising a virus-like particle (VLP) derived from John Cunningham virus (JCV), a drug delivery system and novel VLP obtainable by said method. The method comprises steps of disassembly of VLP into pentamers and reassembly into VLP.

The present invention provides a method for restoring immune tolerance in vivo. The invention relates to the use of a recombinant gene encoding auto-antigens or parts thereof for restoring immune tolerance to the auto-antigens in vivo, under transcriptional control of polyomaviral early and late promoters. In a preferred embodiment, the invention relates to the use of recombinant polyomaviral gene delivery vector particles, such as simian virus 40 (SV40) viral vector particles encoding one or multiple auto-antigens or parts thereof under transcriptional control of the SV40 early and late promoter, for restoring immune tolerance to the auto-antigens in vivo. The invention also relates to compositions comprising recombinant genes or polyomaviral vectors and uses thereof as treatment for degenerative or dystrophic diseases.

The invention relates to a method for providing a drug delivery system, in particular for crossing the blood brain barrier (BBB), comprising a virus-like particle (VLP) derived from John Cunningham virus (JCV), a drug delivery system and novel VLP obtainable by said method. The method comprises steps of disassembly of VLP into pentamers and reassembly into VLP.

Provided are particles of nucleic acid origami structure encapsulated by at least twelve capsid units, compositions comprising the same and uses thereof for delivery of nucleic acids to target cells.

The present invention provides an integration-defective lentiviral vector based on a parental lentivirus and related methods, the integration-defective lentiviral vector including one or more of the following: (a) a mutation, deletion or other modification of one or more binding sites for a host factor involved in gene silencing; (b) an addition of one or more binding sites for a transcription activator, which can be natural (such as but not limited to ubiquitous and/or tissue/cell type specific) including but not limited to SP1 NFkB, or synthetic including but not limited to binding sites for tetracycline regulated trans activators tTA, rtTA, tT65, and/or rtT65; (c) one or more nucleic acid sequences from a SV40 genome, wherein the one or more sequences are obtained from a region of the SV40 genome upstream to the SV40 poly-adenylation signal; (d) a shRNA expression cassette, which encodes a shRNA directed to a host gene involved in epigenetic silencing and/or in DNA repair pathways; or (e) any combination of (a), (b), (c) and (d), wherein as compared to the parental lentivirus, the integration-defective lentiviral vector resists gene silencing.