The present invention relates to adeno-associated virus capsid polypeptide sequences and their use in therapeutic transgene delivery to the eye and potentially other tissues.

This application discloses the compositions comprising biologically active synthetic nanoparticle constructs and methods of use thereof to modify gene expression including transcriptional activation and transcriptional repression.

The present invention relates to nucleic acid molecules comprising a nucleic acid sequence encoding a membrane-bound biotin mimetic peptide (BMP) or biotin acceptor peptide (BAP). The invention also relates to a method for selection of high producer cells secreting a protein of interest.

A method of using a virus-like particle from a polyomavirus having a first nucleic acid as a cargo to detect a second nucleic acid. The method includes providing the virus-like particle from the polyomavirus having the first nucleic acid as the cargo, and detecting, via the virus-like particle from the polyomavirus, the second nucleic acid.

The disclosure provides methods and compositions for delivering polynucleotides into cells. The disclosure provides transiently protected polynucleotides comprising an anionic charge-neutralizing moiety/group, which may also confer additional functionality. These compounds can enter the cytosol of cells by endocytic or macropinocytic mechanisms. The transient protecting group is bioreversible, i.e., once inside a cell, it is designed to be removed by enzymatic activity or by passive intracellular methods (e.g., changes in pH or reductive environment).

Provided are 9-base morpholino antisense compounds targeted to polyCUG repeats in the 3UTR region of dystrophia myotonica protein kinase (DMPK) mRNA, and related methods for treating myotonic dystrophy DM1.

The present invention relates to an adeno-associated virus (AAV), comprising an insertion of at least 6-8 amino acids between the positions corresponding to position 587 and 588 of SEQ ID NO: 1. Also envisioned are AAVs of the present invention for use as a medicament and pharmaceutical compositions comprising the AAV of the present invention. Further, the present invention relates to an in vitro use of AAV of the present invention for transduction of the nucleus of retinal cells. Also concerned is a method for screening an insertion sequence as well as a peptide obtainable by the method for screening. Also contemplated are kits comprising the AAV of the present invention.

Modified capsid proteins containing at least a portion of hepatitis E virus (HEV) open reading frame 2 (ORF2) having one or more cysteine residues in a surface variable loop or the C-terminus of HEV ORF2, or a portion thereof, are provided. The modified capsid proteins can be used to form hepatitis E virus (HEV) virus like particles (VLPs) having cysteine functional groups exposed on the outer-surface. The exposed cysteine functional groups can be modified via their thiol reactive group. For example, a bioactive agent, such as a cell-targeting ligand, can be conjugated to the one or more cysteines for targeted delivery of chemically activated nanocapsids.

The present invention is a peptide lock that comprises at least one peptide that is genetically encoded into the Adeno-associated virus (AAV) capsid that block biologically active domains on the virus capsid surface. The peptide lock, can be processed by biological enzymes to restore biological behavior of the capsid-displayed domains, thus decoding the lock or opening the lock. A method of forming the peptide lock comprises providing at least one peptide, providing an Adeno-associated virus capsid and genetically inserting the at least one peptide into the Adeno-associated virus capsid to block the biologically active domains on the virus capsid surface.

The present invention is directed to protocells for specific targeting of hepatocellular and other cancer cells which comprise a nanoporous silica core with a supported lipid bilayer; at least one agent which facilitates cancer cell death (such as a traditional small molecule, a macromolecular cargo (e.g. siRNA or a protein toxin such as ricin toxin A-chain or diphtheria toxin A-chain) and/or a histone-packaged plasmid DNA disposed within the nanoporous silica core (preferably supercoiled in order to more efficiently package the DNA into protocells) which is optionally modified with a nuclear localization sequence to assist in localizing protocells within the nucleus of the cancer cell and the ability to express peptides involved in therapy (apoptosis/cell death) of the cancer cell or as a reporter, a targeting peptide which targets cancer cells in tissue to be treated such that binding of the protocell to the targeted cells is specific and enhanced and a fusogenic peptide that promotes endosomal escape of protocells and encapsulated DNA. Protocells according to the present invention may be used to treat cancer, especially including hepatocellular (liver) cancer using novel binding peptides (c-MET peptides) which selectively bind to hepatocellular tissue or to function in diagnosis of cancer, including cancer treatment and drug discovery.