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

Compositions and methods are provided for modifying a genomic locus of interest in a eukaryotic cell, a mammalian cell, a human cell or a non-human mammalian cell using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Further methods combine the use of the LTVEC with a CRISPR/Cas system. Compositions and methods for generating a genetically modified non-human animal comprising one or more targeted genetic modifications in their germline are also provided.

Compositions and methods for delivering non-anionic polynucleotide analog cargoes to the cytosolic/nuclear compartment of eukaryotic cells via a synthetic peptide shuttle agent are described herein. The non-anionic polynucleotide analog cargoes may be charge-neutral or cationic, and the synthetic peptide shuttle agent is a peptide comprising an amphipathic alpha-helical motif having both a positively-charged hydrophilic outer face and a hydrophobic outer face, wherein synthetic peptide shuttle agent is not covalently linked, or linked in a cleavable manner under physiological conditions, to the non-anionic polynucleotide analog cargoes. The non-anionic polynucleotide analog cargo may be a charge-neutral or cationic antisense synthetic oligonucleotide (ASO) that hybridizes to an intracellular target RNA for gene expression modification.

The present disclosure provides adeno-associated virus (AAV) virions with altered capsid protein, where the AAV virions exhibit greater infectivity of retinal cells, when administered via intravitreal injection, compared to wild-type AAV. The present disclosure further provides methods of delivering a gene product to a retinal cell in an individual, and methods of treating ocular disease.

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 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.

The present disclosure provides a non-naturally occurring CRISPR-Cas system comprising: a Cas9 effector protein capable of generating cohesive ends (stiCas9), and a guide polynucleotide that forms a complex with the stiCas9 and comprising a guide sequence, wherein the guide sequence hybridizes with a target sequence in a eukaryotic cell but does not hybridize to a sequence in a bacterial cell, and wherein the complex does not occur in nature. The present disclosure also provides a method of introducing a sequence of interest into a chromosome of a cell. Finally, the present disclosure provides for a method of modifying one or more nucleotides using seamless mutagenesis.

Provided are engineered phages populations, which are homogeneous in length, as well as methods of making and methods of using such phages. Also provided are engineered chlorotoxin-phages as well as their methods of making and using. The disclosed homogeneous phage populations and chlorotoxin-phages may be used, for example, for treating and/or imaging tumors, such as central nervous system tumors.

Provided are engineered phages populations, which are homogeneous in length, as well as methods of making and methods of using such phages. Also provided are engineered chlorotoxin-phages as well as their methods of making and using. The disclosed homogeneous phage populations and chlorotoxin-phages may be used, for example, for treating and/or imaging tumors, such as central nervous system tumors.

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.