Abstract: The present invention pertains to a new nanoparticle-like delivery system for intracellular delivery of cargo molecules such as nucleic acids, ribonucleoproteins and extracellular vesicles.

Abstract: The present invention pertains to inter alia methods for purifying extracellular vesicles including exposing a sample comprising at least one extracellular vesicle to ultrafiltration; and exposing the sample following the ultrafiltration in step (i) to size exclusion liquid chromatography.

Abstract: The present invention pertains to inter alia methods for purifying extracellular vesicles including exposing a sample comprising at least one extracellular vesicle to ultrafiltration; and exposing the sample following the ultrafiltration in step (i) to size exclusion liquid chromatography.

Abstract: The present invention pertains to inter alia therapeutic delivery vesicles, for instance exosomes or microvesicles, comprising polypeptide constructs, methods for producing said therapeutic delivery vesicles, pharmaceutical compositions and medical uses thereof. The therapeutic polypeptide constructs comprised in the extracellular delivery vesicles enable sequestering target molecules of interest, to treat e.g. neuro-inflammatory diseases and cancer.

Abstract: The present invention relates to anti-gene oligonucleotides adapted to hybridize to DNA in a HTT gene, which are based on locked nucleic acids, phosphorodiamidate morpholino oligomers, (PMO) or equivalent oligonucleotide analogues comprising a (CAG)n sequence, and whose target is a sequence where the majority of the repeats are CAG/CTG, for use in down regulating the expression of the HTT gene, resulting in reduced HTT mRNA and protein levels in afflicted subjects, or in diagnosis, treatment and/or prevention of Huntington's disease, and where the anti-gene oligonucleotides target non-canonical DNA structures, including hairpin and cruciform. The invention also relates to a delivery system comprising said oligonucleotides and said use thereof.

Abstract: The present invention relates to anti-gene oligonucleotides adapted to hybridize to DNA in a HTT gene, which are based on locked nucleic acids, phosphorodiamidate morpholino oligomers, (PMO) or equivalent oligonucleotide analogues comprising a (CAG)n sequence, and whose target is a sequence where the majority of the repeats are CAG/CTG, for use in down regulating the expression of the HTT gene, resulting in reduced HTT mRNA and protein levels in afflicted subjects, or in diagnosis, treatment and/ or prevention of Huntington's disease,and where theanti-gene oligonucleotides target non-canonical DNA structures, including hairpin and cruciform. The invention also relates to a delivery system comprising said oligonucleotides and said use thereof.

Abstract: The present invention pertains to inter alia therapeutic delivery vesicles, for instance exosomes or microvesicles, comprising polypeptide constructs, methods for producing said therapeutic delivery vesicles, pharmaceutical compositions and medical uses thereof. The therapeutic polypeptide constructs comprised in the extracellular delivery vesicles enable sequestering target molecules of interest, to treat e.g. neuro-inflammatory diseases and cancer.

Abstract: The use of at least one nucleic acid based nuclear localization signal including a natural or synthetic m3G-CAP is shown to increase transmembrane transport of a molecular cargo, in particular large molecules, into the nucleus. The use of natural and synthetic m3G-CAP is disclosed and the effect shown with a natural RNA 5? end nuclear localization signal composed of a 2,2,7-trimethylguanosine CAP (m3G-CAP) coupled to fluorescent Streptavidin in one example, and an antisense oligonucleotide in another. A methylenephosphonate modified m3G-CAP is shown to have improved stability in human serum and in cytosolic extract.

Abstract: The use of at least one nucleic acid based nuclear localization signal including a natural or synthetic m3G-CAP is shown to increase transmembrane transport of a molecular cargo, in particular large molecules, into the nucleus. The use of natural and synthetic m3G-CAP is disclosed and the effect shown with a natural RNA 5? end nuclear localization signal composed of a 2,2,7-trimethylguanosine CAP (m3G-CAP) coupled to fluorescent Streptavidin in one example, and an antisense oligonucleotide in another. A methylenephosphonate modified m3G-CAP is shown to have improved stability in human serum and in cytosolic extract.

Abstract: A method for the production of a biomolecular complex having at least two functional elements each attached to a target molecule or area through binding elements, wherein each functional element is attached to a specific binding element, the binding element being a nucleotide sequence and the target molecule or area comprising the corresponding target sequence, and the target molecules or areas being separated from each other by a first linker or spacer and an optional second linker, the linkers being nucleic acid polymers having a pre-determined physical property.

Abstract: A Z-shaped construct having the capacity to hybridize to double stranded DNA in a trans fashion to affect transcription is produced from at least two oligonucleotides, connected to each other, wherein the oligonucleotides are connected to one another through one of sequence specific Watson-Crick base pairing; a covalent linker or a covalent bond directly between the backbones or the bases of said oligonucleotides; or a non-covalent linker or a non-covalent bond directly between the backbones or the bases of said oligonucleotides.

Abstract: The present invention relates to modification of nucleic acids for specific delivery in vitro and in vivo. More specifically, the present invention relates to modification of RNA or DNA molecules in order to add functions in terms of delivery and specificity to RNA interference or antisense technology. A specific binding domain is incorporated into the nucleic acid to which a complementary nucleic acid, conjugated to a biologically active molecule, can hybridize.

Abstract: A synthetic transport entity is used for transferring a nucleic acid sequence of interest across a biological membrane. The transport entity comprises a functional element (FE), which increases the efficiency of transfection (e.g. polyethylene glycol (PEG) or a nuclear localisation signal), a binding element (BE), such as a peptide nucleic acid (PNA), and a carrier molecule comprising the nucleic acid of interest and a BE target sequence. The transport entity can be altered in a controlled manner at the surface of the membrane or after having passed across the membrane or having been taken up by the cell, and comprises at least one alteration site that, when altered, changes a property of the transport entity.

Abstract: The present invention concerns biomolecular complexes and in particular a method for linking biomolecules in sets of two or more, with predefined three-dimensional orientation and spacing between the two or more biomolecules. The linking method has application in the construction of novel, highly specific vehicles for drug delivery, e g in gene therapy, and in the construction and performing of assays for the study of biomolecular interaction, e g receptor-ligand interaction studies.

Abstract: The present invention relates to a method of introducing organic molecules carrying genetic information into isolated target cells, which comprises the step of passing a supernatant comprising said organic molecules through a fluidized collection of said target cells during an essentially constant flow. The fluidisation is provided by directing a flow of the supernatant so as to essentially counteract the gravitational force of the target cells, or alternatively a force applied thereon. Thus, the present method enables an efficient introduction of genetic information into the target cells.

Abstract: The present invention relates to a novel method of genetic modification, wherein a nucleic acid of interest is transferred across a biological membrane, and/or directed to a specific location within or on a cell, by use of a synthetic transport entity. The transport entity according to the invention is new as such and produced by coupling a functional element (FE), such as a nuclear localization signal (NLS), an antennapedia peptide of a protein comprising both membrane translocation and nuclear transport properties, to a binding element (BE), such as a peptide nucleic acid (PNA), preferably separated by a linker molecule, which combination is then hybridized to a BE target sequence present on a carrier, which also includes the nucleic acid of interest. The present nucleic acid of interest may for example be a gene encoding a peptide, a protein or an RNA, or any other nucleic acid useful in genetic recombination events.

Abstract: The present invention relates to a method of introducing organic molecules carrying genetic information into isolated target cells, which comprises the step of passing a supernatant comprising said organic molecules through a fluidized collection of said target cells during an essentially constant flow. The fluidisation is provided by directing a flow of the supernatant so as to essentially counteract the gravitational force of the target cells, or alternatively a force applied thereon. Thus, the present method enables an efficient introduction of genetic information into the target cells.