Abstract: The present invention provides an artificial nucleic acid for site-directed editing of a target RNA with enhanced editing specificity and avoiding undesirable off-target editing. The artificial nucleic acid comprises a targeting sequence comprising a nucleic acid sequence complementary to or at least partially complementary to a target sequence in the target RNA comprising one or more nucleotides to be edited, wherein the targeting sequence is flanked by a first recruiting moiety capable of recruiting a deaminase, and a second recruiting moiety capable of recruiting a deaminase, wherein at least one of the first and second recruiting moiety comprises at least one recruitment sequence, and preferably comprises at least two recruitment sequences, which bind(s) to complementary region(s) in the target RNA.

Abstract: The invention is directed to a gene editing system for editing genomic DNA to modulate splicing, a polynucleotide or vector encoding said gene editing system, a lipid particle comprising said gene editing system, a pharmaceutical composition comprising said gene editing system polynucleotide or vector or lipid particle, methods of editing genomic DNA in a cell to modulate splicing, and a cell processed by said methods.

Abstract: The present invention relates to a gene editing system for editing the arylsulfatase A (ARSA) gene, polynucleotides, sgRNA molecules and repair templates which may form parts of the gene editing system, vectors and host cells incorporating said nucleic acid molecules, a pharmaceutical composition, and kits. It also relates to a method of gene editing the arylsulfatase A (ARSA) gene in a cell or a subject, and to a method of treating a disease or disorder associated with functional deficiency of the ARSA enzyme in a subject.

Abstract: The present invention provides a novel bispecific anti-CD28 antibody format which is bivalent and comprises two CD28 binding sites, and at least one target binding site. The bispecific anti CD28 antibody of the invention is surprisingly advantageous due to its costimulatory activity which is strictly target cell restricted. The bispecific CD28 antibody of the invention is provided for use in the treatment of diseases either alone or in combination with a further bispecific antibody inducing a CD3/T cell receptor signal.

Abstract: The present invention relates to imidazo[4,5-c]quinoline compounds and to their use in the inhibition, regulation and/or modulation of signal transduction by ATM kinase and, in particular, for the treatment of ATM mediated diseases, especially cancer.

Abstract: The present invention relates to a protein having G-CSF-like activity comprising a) one or two polypeptide chains; b) a bundle of four ?-helices; and c) two or three amino acid linkers that connect contiguous bundle-forming ?-helices that are located on the same polypeptide chain, wherein each amino acid linker has a length between 2 and 20 amino acids. The invention also provides for a polynucleotide and a vector encoding the protein of the invention, host cells comprising said polynucleotide, a method for producing the protein of the invention and a pharmaceutical composition comprising the protein of the invention. The invention further relates to uses of the proteins of the invention as a research reagent and the use of the protein and/or pharmaceutical composition comprising the same as a medicament, e.g., for use in increasing stem cell production, for use in inducing hematopoiesis and/or for use in mobilizing hematopoietic stem cells.

Abstract: The present invention provides a novel PSMA binding antibody termed 10B3 and pharmaceutical and diagnostic uses of the antibody 10B3. The PSMA antibody 10B3 does not cross-compete with the state of the art PMSA binding antibody J591 and has a reduced induction of antigen shift compared to J591 and a unique reactivity with squamous cell carcinoma (SCC) cells of different origin.

Abstract: The present invention relates to novel inhibitors of the shikimate pathway (shikimic acid pathway), pharmaceutical compositions comprising these novel inhibitors, methods for the production of the inhibitors and their use as antibiotics and herbicides.

Abstract: The present invention relates to a method for determining in a subject's biological sample the relative proportions of papillary renal cell carcinoma (pRCC), clear cell renal cell carcinoma (ccRCC), and chromophobe renal cell carcinoma (chRCC), an array comprising capture molecules capable of specifically binding to RCC signature genes or coding sequences thereof or products encoded thereby, and the use of RCC signature genes for classifying a subject into a renal cell carcinoma (RCC) risk group and/or for determining in a subject's biological sample the relative proportions of pRCC, ccRCC, and chRCC.

Abstract: In a method for examining the faculty of hearing for at least one ear of a mammal, in which growth curves are determined on the basis of the measurement of DPOAE's evoked by pairs of excitation signals (f1, f2) for different excitation frequencies f2, the ear is presented with first excitation signals with a first excitation frequency f1 and a first noise level L1 and secondary excitation signals with a second excitation frequency f2 and a second noise level L2. Pulse pairs with a first pulse of the first excitation signal and a second pulse of the second excitation signal are presented in the ear, and the DPOAE's evoked thereby are captured and evaluated. A set of at least two different pulse pairs with different second excitation frequencies f2 is presented in one block that is repeated several times during a measuring period.

Abstract: The present invention relates to a nucleotide-modified messenger RNA for the permanent correction of a genetic alteration on a DNA. The invention further relates to a nucleotide-modified messenger RNA in combination with a repair template. It also relates to a pharmaceutical composition. It finally relates to methods for the correction of a genetic alteration on a DNA.

Abstract: The invention relates to compositions and methods that utilize polymeric nanoparticles to deliver a therapeutic compound to ocular cells or ocular tissue. Provided is a drug-loaded micelle comprising self-assembled amphiphilic biopolymers, such as hydrophobically modified nucleic acids or polypeptides, for use as ophthalmic drug delivery system. Also provided are ophthalmic compositions and methods for preventing or treating an ophthalmic disease.

Abstract: In a hearing aid (26) that can be inserted into the ear canal (12) of a patient, comprising an actuator (31) effecting a mechanical stimulation of the tympanic membrane (14), the actuator (31) comprises an inner surface (32) associated with the tympanic membrane (14) and an outer surface (42) associated with the ear canal (12) and is configured as an areal disk actuator, whose deformation stimulates the tympanic membrane (14) by areal deformation. On the actuator (31) at a distance from the outer surface (42) a cover plate (43) is arranged which together with the outer surface (42) delimits a preferably lenticular cavity (48).

Abstract: The invention relates to plants with increased resistance to plant pathogens, wherein the intracellular concentration of inositol pyrophosphate InsP7 and/or InsP8 in said plants is increased in comparison to the wild-type plant. In particular, the invention involves plants with increased expression of at least one protein involved in the synthesis of inositol pyrophosphates InsP7 and/or InsP8, such as, for example, proteins VIH2 and VIH1. The plants according to the invention are particularly resistant to the following plant pathogens: herbivore insects, for example larvae of agriculturally relevant pests, pathogenic fungi, such as necrotrophic fungi, or other plant pests, such as biotrophic pathogens. The invention further relates to the method for increasing plant resistance to plant pathogens, wherein the intracellular concentration of inositol pyrophosphates InsP7 and/or InsP8 is increased in comparison to the wild-type plant.

Abstract: The present invention relates to a method of identifying a predisposition for developing type 2 diabetes mellitus in a subject, said method comprising the step of assessing in a sample obtained from said subject the amount of one or more metabolite(s) selected from (a) a first group comprising the metabolites glycine, lysoPhosphatidylcholine acyl C18:2, lysoPhosphatidylcholine acyl C17:0, lysoPhosphatidylcholine acyl C18:0, lysoPhosphatidylcholine acyl C18:1, phosphatidylcholine acyl-alkyl C34:2, phosphatidylcholine acyl-alkyl C36:2, phosphatidylcholine acyl-alkyl C36:3 and isobaric metabolites having the same molecular mass as glycine, lysoPhosphatidylcholine acyl C18:2, lysoPhosphatidylcholine acyl C17:0, lysoPhosphatidylcholine acyl C18:0, lysoPhosphatidylcholine acyl C18:1, phosphatidylcholine acyl-alkyl C34:2, phosphatidylcholine acyl-alkyl C36:2 or phosphatidylcholine acyl-alkyl C36:3 but different chemical formula; and/or (b) a second group comprising the metabolite acetylcarnitine C2 and an isobaric m

Abstract: The present invention relates to a nucleotide-modified messenger RNA for the permanent correction of a genetic alteration on a DNA. The invention further relates to a nucleotide-modified messenger RNA in combination with a repair template. It also relates to a pharmaceutical composition. It finally relates to methods for the correction of a genetic alteration on a DNA.

Abstract: A device for measuring the elasticity of a macroscopic sample, in particular for measuring the elasticity of tissue of a living human or animal, is disclosed, which comprises the following: at least one outlet for a jet of fluid and/or one inlet for aspiration of a stream of fluid, means for positioning the device in relation to the macroscopic sample in such a way that the outlet and/or the inlet and/or an end face of the device is at a predetermined distance from the macroscopic sample, or at a distance therefrom that can be determined by said means, and a mechanism for measuring a variable that is characteristic of the extent of a deformation of the sample on account of an interaction of the sample with the jet of fluid and/or the aspirated stream of fluid, wherein this variable is determined by an ion current in the deformation area of the sample, or the volumetric flow of the fluid itself, or, if the fluid is enclosed by the elastic sample, by a change of volume and associated change of pressure in the e

Abstract: The present invention relates to a method of treating movement disorders of a living being, a method of treating refractory gait disturbances of a human Parkinson's disease patient being affected by gait disturbances, and an apparatus for deep brain stimulation (DBS) of a living being affected by movement disorders.

Abstract: The present invention relates to a nucleic acid molecule, a genetic construct, siRNA molecules and a composition which comprises the nucleic acid molecule and/or the genetic construct and/or the siRNA molecules and can be used for inhibition of the expression of endothelial adhesion molecules. The invention also relates to a device, which is coated with the aforementioned molecules, the composition or the construct, or contains them. The present invention further relates to a corresponding use of the nucleic acid molecule, of the genetic construct or of the siRNA molecules and a method of inhibition of the expression of adhesion molecules and a method of vessel grafting, lung transplantation, treatment of lung transplants, and a method of treatment of the open heart within the scope of cardioplegia.

Abstract: The present invention relates to a method for the in vitro determination of the presence of or a predisposition of a patient to the development of cancer. In the method according to the invention, the presence of a marker is determined in a biological sample of the patient, said marker being selected from a) the amino acid sequence SEQ ID No. 2 from the sequence protocol that is provided, or b) a nucleic acid that encodes the amino acid sequence with the SEQ ID No. 2. The invention further relates to the amino acid and the encoding nucleic acid and to the use thereof in diagnostics and for molecular therapeutic approaches.