The present disclosure provides targeting peptides and vectors containing a sequence that encodes targeting peptides that deliver agents to the brain.

The invention relates to a peptide, polypeptide, or protein that binds specifically to cells of the lung endothelium. The peptide, polypeptide, or protein can be a component of a viral capsid and can be used to lead a recombinant viral vector selectively to the lung endothelial tissue after systemic administration to a subject and to ensure tissue-specific expression of one or more transgenes there. The invention thus further relates to a recombinant viral vector, preferably an AAV vector, which comprises a capsid comprising the peptide, polypeptide, or protein according to the invention and which comprises at least one transgene packaged in the capsid. The viral vector is suitable in particular for the therapeutic treatment of a lung disorder or a lung disease. The invention further relates to cells and pharmaceutical compositions which comprise the viral vector according to the invention.

A printed circuit board according to an embodiment comprises: an insulating layer; a circuit pattern disposed on the upper surface of the insulating layer; a support layer which is disposed on the upper surface of the insulating layer to expose the upper surface of the circuit pattern and is in contact with the sides of the circuit pattern; and a protective layer disposed on the upper surfaces of the support layer and the circuit pattern, wherein the upper region of the insulating layer comprises a first region and a second region, and the protective layer comprises an open region exposing the upper surfaces of the support layer and the circuit pattern that are disposed in the first region, and the support layer comprises a first upper surface positioned at the highest level among the upper surfaces of the support layer and a second upper surface positioned at the lowest level among the upper surfaces of the support layer, the second upper surface being lower than the first upper surface, and the protective layer comprises a first portion which contacts the upper surface of the circuit pattern of the first region and a second portion which contacts the upper surface of the support layer of the first region, and the second portion of the protective layer contacts the second upper surface of the support layer and includes a first lower surface which is lower than the upper surface of the circuit pattern.

The disclosure provides, in some aspects, compositions (e.g., isolated nucleic acids and rAAVs) comprising a transgene which encodes at least one inhibitory nucleic acid which decreases expression of a gene encoding a serine palmitoyltransferase protein (e.g., SPTLC1). In some aspects, the disclosure relates to methods of treating hereditary sensory and autonomic neuropathy 1 (HSAN1) by administering the compositions described by the disclosure to a cell or subject.

Disclosed herein are methods and compositions for insertion of transgene sequences encoding proteins involved in clotting into the genome of a cell for treating conditions including hemophilias.

The present disclosure provides adeno-associated virus (AAV) virions with altered capsid protein that binds heparan sulfate proteoglycans, where the AAV virions exhibit greater infectivity of retinal cells, altered tropism and/or the ability to bind and cross the inner limiting membrane following intravitreal injection. The present disclosure further provides methods of delivering a gene product to a retinal cell in an individual, and methods of treating ocular disease.

Provided herein are variant adeno-associated virus (AAV) capsid proteins having one or more modifications in amino acid sequence relative to a parental AAV capsid protein, which, when present in an AAV virion, confer increased infectivity of one or more types of muscle cells as compared to the infectivity of the muscle cells by an AAV virion comprising the unmodified parental AAV capsid protein. Also provided are recombinant AAV virions and pharmaceutical compositions thereof comprising a variant AAV capsid protein as described herein, methods of making these rAAV capsid proteins and virions, and methods for using these rAAV capsid proteins and virions in research and in clinical practice, for example in, e.g., the delivery of nucleic acid sequences to one or more muscle cells for the treatment of muscle disorders and diseases.

The present disclosure provides adeno-associated virus (AAV) virions with altered capsid protein that binds heparan sulfate proteoglycans, where the AAV virions exhibit greater infectivity of retinal cells, altered tropism and/or the ability to bind and cross the inner limiting membrane following intravitreal injection. The present disclosure further provides methods of delivering a gene product to a retinal cell in an individual, and methods of treating ocular disease.

The invention is directed to the field of gene therapy, i.e. gene delivery into target cells, tissue, organ and organism, and more particularly to gene delivery via viral vectors. The inventors showed that it is possible by chemical coupling to modulate the coupling of a ligand in the surface of the capsid of AAV, for example AAV2 and AAV3b. In particular, the present invention relates to a recombinant Adeno-Associated Virus (rAAV) vector particle having at least one primary amino group contained in the capsid proteins, chemically coupled with at least one ligand L wherein coupling of said ligand L is implemented through a bond comprising a —CSNH— bond and an optionally substituted aromatic moiety.

Particularly, the inventors tested the chemical coupling of mannose ligand on AAV2 for subretinally injection to rats. The present invention further relates to a method for chemically coupling an Adeno-Associated Virus (AAV) vector particle with at least one ligand L and to a Recombinant Adeno-Associated Virus (rAAV) vector particle obtained by said method as well as a pharmaceutical composition comprising it and their corresponding medical use.

Described herein is an adeno-associated virus (AAV) capsid polypeptide bonded to a binding peptide including an amino acid sequence RGDX1X2X3X4, with X1 to X4 being independently selected amino acids, for use in treating and/or preventing a muscular disease and/or in muscle regeneration. Also described are polynucleotides, host cells, adeno-associated virus (AAV) capsids, pharmaceutical compositions, uses, and methods related to the AAV capsid polypeptide.