The present invention is directed to non-naturally occurring peptides containing a membrane-penetrating amino acid sequence and further at least one polycationic moiety or peptide sequence. The peptides are suitable for use in delivery a cargo to the interior of a cell. Suitable cargo includes nucleic acid molecules (including DNA, RNA or PNA), polypeptides, or other biologically active molecules. The present invention is further directed to transfection complexes containing the non-naturally occurring peptides of the present invention in non-covalent association with at least one cationic lipid and a cargo to be delivered to the interior of a cell. The invention further relates to methods for the preparation and use of the non-naturally occurring peptides for the formation of transfection complexes and the delivery of a cargo to the interior of a cell in culture, an animal or a human. The invention also relates to compositions and kits useful for transfecting cells.

The invention discloses a human adenovirus species C having a capsid which comprises a modified adenovirus hexon protein, wherein the modified adenovirus hexon protein has a modified HVR1 region, wherein the modified HVR1 region has the sequence DEAATALEINLKKKKQAEQQ (SEQ ID NO.: 1). The invention further discloses the adenovirus of the disclosure for use in treating or preventing a human disease. The invention further discloses a nucleic acid encoding the modified adenovirus hexon protein. The invention further discloses the use of an adenovirus according to the disclosure for transducing mesenchymal stromal cells (MSCs) or tumor cells. The invention further discloses an in vitro method for transducing MSCs and a transduced MSC obtainable by the method. The invention further discloses the transduced MSC of the disclosure for use in treating a disease.

Disclosed are systems and methods for detecting extracellular ligands and/or inducing expression of an exogenous or endogenous gene. The disclosed systems and methods typically include and/or utilize (i) first and second exogenous extracellular sensors, and third and fourth exogenous extracellular sensors; and (ii) an expression vector comprising a target gene operably linked to a hybrid promoter sequence. The hybrid promoter sequence of the expression vector includes a minimal promoter for inducing transcription and the hybrid promoter sequence further includes interspaced transcription regulator binding sites upstream of the minimal promoter that bind two or more transcription regulators of the extracellular sensors that are released from the extracellular sensors when the extracellular sensor bind an extracellular ligand.

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.

The present application relates to (i) a variant adeno-associated virus (AAV) capsid polypeptide comprising a peptide insertion in the variable region IV or in the variable region VIII relative to a wild-type AAV capsid polypeptide, wherein the peptide insertion comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-29 or an amino acid sequence having at least 70% sequence identity thereto, (ii) an isolated nucleic acid encoding the aforementioned variant polypeptide, (iii) a recombinant polynucleotide comprising the aforementioned nucleic acid, and (iv) an isolated cell comprising the aforementioned polypeptide, nucleic acid or recombinant polynucleotide. The present application further relates to (v) an adeno-associated virus (AAV) vector comprising the aforementioned variant polypeptide, (vi) a pharmaceutical composition comprising the aforementioned AAV vector as well as (vii) the use of the aforementioned vector or pharmaceutical composition in preventing or treating an ocular disease. Finally, the present application relates to (viii) a method of delivering a heterologous nucleic acid to a retinal cell and (ix) a method of delivering a heterologous nucleic acid to the eye of a subject.

The present disclosure relates to methods, kits, and compositions for improving the efficiency of homologous recombination. In particular, the disclosure relates to methods for cloning DNA molecules directly into a genome with the combined use of promoter trapping and short homology arms, nuclear localization signal, and/or binding one or more DNA binding agents (TAL effector domain or truncated guide RNA bound by Cas9) to specific sites thereby displacing or restructuring chromatin at the target locus, and/or it increasing the accessibility of the target locus to further enzymatic modifications. The methods and compositions provided herein are, inter alia, useful for genome editing and enhancing enzymatic processes involved therein.