The present disclosure relates, according to some embodiments, to systems, apparatus, compositions, methods, and workflows that include DNase I variants with desirable properties including, for example, salt tolerance. A DNase I variant, in some embodiments, may have an amino acid sequence that is at least 85% identical, at least 90% identical, at least 95% identical, and/or at least 98% identical to SEQ ID NO:1 and may be identical to SEQ ID NO:1 at one or more positions selected from the group of positions corresponding to L29, A35, D87, Q88, S94, P103, T108, P121, P132, A135, D145, E161, G172, P190, H208, and A224 of SEQ ID NO:1.

The present technology provides methods and compositions for the treatment of inflammatory and/or tissue damage conditions. In particular, the use of Smad7 compositions delivered locally or systemically to a site of inflammation and/or tissue damage is described. Other specific embodiments concern treatment or prevention of side effects caused by radiation and/or chemotherapy, including but not limited to oral and gastric mucositis. Also provided are codon-optimized nucleic acids encoding for Smad7 fusion proteins.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease encompassing chronic bronchitis, emphysema and remodeling of small airways that can be treated by the caveolin-1 peptide CSP7 (SEQ ID NO:1). Chronic tobacco smoke exposure (TSE)-induced lung injury includes increased alveolar and airway inflammation, type II alveolar epithelial cells (A.sub.2Cs) senescence and apoptosis, and mucus hypersecretion by AECs. Interleukin 17A-mediated induction of plasminogen activator inhibitor-1 (PAI-1) expression through caveolin-1 led to TSE-induced lung injury, which was abrogated by CSP7 treatment which abolished A.sub.2Cs senescence and apoptosis, and AECs mucus hypersecretion in TSE wild type (WT) mice. Ex vivo CSP7 treatment of lung tissue of COPD patients decreased A.sub.2C apoptosis and AEC mucus hypersecretion. Lung injury induced by PAI-1 expression in COPD lung tissue and WT mice (20 weeks TSE), with A.sub.2Cs senescence and apoptosis, and AEC mucus hypersecretion was abolished by CSP7.

An antitumor peptide provided according to the present invention includes (1) an S1PR-TM related sequence; and (2) an amino acid sequence functioning as a cell penetrating peptide; wherein the total number of amino acid residues is 100 or less.

The present application provides: a polypeptide characterized by having an ability of penetrating into a cell and the structure represented by Formula (I) ##STR00001##
wherein n is a number of 2 to 20; R.sup.1 and R.sup.2 may independently represent a C.sub.1-C.sub.4 alkyl group or may bind to each other to form a ring; R.sup.3 represents a C.sub.1-C.sub.10 primary aminoalkyl group; R.sup.4 represents a hydrogen atom or a C.sub.1-C.sub.10 hydrocarbon group; the “n” number of R.sup.1, R.sup.2, R.sup.3, and R.sup.4 may independently be the same with or different from each other; and the N-terminus and the C-terminus may or may not be modified independently; and a cell-invasive composition comprising the polypeptide and a substance of interest.

A multimerization delivery system that can be used to deliver a cargo molecule intracellularly. The multimerization delivery system can achieve high-efficiency endocytosis of a cargo molecule and high-efficiency release thereof from an endocytic vesicle, significantly improving the cytoplasmic delivery efficiency of the cargo molecule. Once the cargo molecule is available in the cytoplasm, the cargo molecule can play any role related thereto. The multimerization delivery system provides an effective means for affecting the biological mechanisms and pathways of cells, and can be used in various fields such as research, treatment, and diagnosis.

The invention provides variants of a previously described active agent for treating stroke, Tat-NR2B9c, in which target binding characteristics are retained by inclusion of L-amino acids at the C-terminus and plasmin-resistance is conferred by inclusion of D-amino acids elsewhere. An exemplary agent has the sequence ygrkkrrqrrrklssIETDV (SEQ ID NO:62). The resulting active agents have several advantages including administration at the same time as thrombolytic agents without significant loss of activity due to plasmin digestion. The resulting agents are also more suitable for administration by alternative routes to intravenous infusion, such as subcutaneous, intranasal and intramuscular, and for multi-dosing regimes for treatment of chronic conditions.

A cell penetrating peptide (CPP) according to the present invention is a novel cationic cell penetrating peptide that can effectively transport a biologically active molecule by passing through a cell membrane even when a biologically active molecule is bound thereto, and compared with conventional CPPs, it has excellent cell permeability enabling the transport of a biologically active molecule into cells, and the delivered biologically active molecule may effectively maintain its activity in cells. Accordingly, the CPP of the present invention may be very useful in various fields including cosmetics, diagnostics, drug delivery systems, recombinant protein vaccines, DNA/RNA therapeutics, and gene and protein therapy.

Disclosed herein are uses of a polypeptide comprising NIMoEsh to treat a disease or condition associated with acute myocardial infarction (AMI) in a subject in need thereof, of a polypeptide comprising NIMoEsh to restore heart function after AMI in a subject in need thereof, of a polypeptide comprising NIMoEsh to reduce or prevent AMI-induced heart function loss in a subject in need thereof, of a polypeptide comprising NIMoEsh to reduce AMI-induced heart tissue infarct in a subject in need thereof, and of a polypeptide comprising NIMoEsh to protect cardiomyocytes against AMI-induced function loss in a subject in need thereof. Disclosed also herein are methods by which such treating, restoring, reducing or preventing, reducing, and/or protecting may be done, and a polypeptide comprising NIMoEsh for use in such treating, restoring, reducing or preventing, reducing, and/or protecting.

Methods and compositions are presented for use in diagnostic, imaging or targeting of therapeutic agents to treat cancer cells in metastases. such as where compositions and methods identify and employ peptides to selectively target cancer cells in metastases in mammals, both in vitro and in vivo.