Peptides are described herein, in particular peptides having antimicrobial properties, as are compositions, articles, and kits comprising such peptides, and methods for using the peptides.

Structurally stabilized, e.g., stapled, peptides with the ability to translocate through microbial cell membranes to the interior of microbial cells and exert a biological activity there are provided, as are methods of designing, making and using such peptides.

Compositions, methods, strategies, kits, and systems for the supercharged protein-mediated delivery of functional effector proteins into cells in vivo, ex vivo, or in vitro are provided. Compositions, methods, strategies, kits, and systems for delivery of functional effector proteins using cationic lipids and cationic polymers are also provided. Functional effector proteins include, without limitation, transcriptional modulators (e.g., repressors or activators), recombinases, nucleases (e.g., RNA-programmable nucleases, such as Cas9 proteins; TALE nuclease, and zinc finger nucleases), deaminases, and other gene modifying/editing enzymes. Functional effector proteins include TALE effector proteins, e.g., TALE transcriptional activators and repressors, as well as TALE nucleases. Compositions, methods, strategies, and systems for the delivery of functional effector proteins into cells is useful for therapeutic and research purposes, including, but not limited to, the targeted manipulation of a gene associated with disease, the modulation of the expression level of a gene associated with disease, and the programming of cell fate.

An improved method of deprotection in solid phase peptide synthesis is disclosed. In particular the deprotecting composition is added in high concentration and small volume to the mixture of the coupling solution, the growing peptide chain, and any excess activated acid from the preceding coupling cycle, and without any draining step between the coupling step of the previous cycle and the addition of the deprotection composition for the successive cycle. Thereafter, the ambient pressure in the vessel is reduced with a vacuum pull to remove the deprotecting composition without any draining step and without otherwise adversely affecting the remaining materials in the vessel or causing problems in subsequent steps in the SPPS cycle.

There are disclosed hybrid proteins comprising at least one signal sequence; at least one DNA binding domain; and at least one cell penetrating peptide (CPP) domain. In embodiments the CPP domain is a TAT domain, and the DNA binding domain is a HU domain. There is also disclosed the use of the hybrid proteins to introduce exogenous DNA into target cells, and methods for introducing exogenous DNA into target cells using the hybrid proteins.

Compositions are described for direct protein delivery into multiple cell types in the mammalian inner ear. The compositions are used to deliver protein(s) (such as gene editing factors) editing of genetic mutations associated with deafness or associated disorders thereof. The delivery of genome editing proteins for gene editing and correction of genetic mutations protect or restore hearing from genetic deafness. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.

The present invention provides RNA-guided endonucleases, which are engineered for expression in eukaryotic cells or embryos, and methods of using the RNA-guided endonuclease for targeted genome modification in in eukaryotic cells or embryos. Also provided are fusion proteins, wherein each fusion protein comprises a CRISPR/Cas-like protein or fragment thereof and an effector domain. The effector domain can be a cleavage domain, an epigenetic modification domain, a transcriptional activation domain, or a transcriptional repressor domain. Also provided are methods for using the fusion proteins to modify a chromosomal sequence or regulate expression of a chromosomal sequence.

Compositions and provided to induce cells of the inner ear to renter the cell cycle and to proliferate. In particular, hair cells are induced to proliferate by administration of a composition which activates the Myc and Notch. Supporting cells are induced to transdifferentiate to hair cells by inhibition of Myc and Notch activity or the activation of Atoh1. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.

The present invention relates to a peptide SSTP1 that modulates IL6 pathway to induce apoptosis in cells where there is overexpression of IL6Rα (Interleukin 6 Receptor). This is achieved by inhibiting IL6/JAK/STAT pathway and/or by activating JNK/AP1 signal transduction pathway. The sensitivity of the cancer cells to SSTP1 was proportional to IL6Rα levels. Further, SSTP1 kills triple negative breast cancer cells, MDA-MB-231, at a concentration that cause neither hemolysis nor cell death to blood cells. The peptide of the present invention utilizes the elements of IL6 pathway and induces apoptosis in cancer cells. SSTP1 functions by activation of JNK/AP1 pathway with concomitant inhibition of STATs, offering a new therapeutic strategy to treat cancer cells that overexpress IL6Rα.

An antimicrobial peptide according to an embodiment of the present disclosure has the amino acid sequence of SEQ ID NO: 1, wherein i) the 1st and the 20th to the 24th amino acids are deleted, ii) the 1st and the 20th to the 24th amino acids are deleted and the 11th or the 18th amino acid is substituted with lysine (K), or iii) the 1st and the 20th to the 24th amino acids are deleted and the 11th and the 18th amino acids are substituted with lysine (K).