520 results about "Cell-penetrating peptide" patented technology

An antisense compound for use in treating myotonic dystrophy DM1 or DM2, a method of enhancing antisense targeting to heart and quadricep muscles, and a method for treating DM1 or DM2 in a mammalian subject are disclosed. The oligonucleotide has 8-30 bases, with at least 8 contiguous bases being complementary to the polyCUG or polyCCUG repeats in the 3′UTR region of dystrophia myotonica protein kinase (DMPK) mRNA in DM1 or DM2, respectively. Conjugated to the oligonucleotide is a cell-penetrating peptide having the sequence (RXRR(B / X)R)2XB, where R is arginine; B is β-alanine; and each X is —C(O)—(CH2)n—NH—, where n is 4-6. The antisense compound is effective to selectively block the sequestration of muscleblind-like 1 protein (MBNL1) and / or CUGBP, in heart and quadricep muscle in a myotonic dystrophy animal model.

Cell-penetrating peptides useful for targeting a therapeutic compound to a selected mammalian tissue, methods for their identification, methods of forming conjugate compounds containing such peptides, and conjugates formed thereby are disclosed. The cell-penetrating peptides are 8 to 30 amino acid residues in length and consist of subsequences selected from the group consisting of RXR, RX, RB, and RBR; where R is arginine, B is β-alanine, and each X is independently —C(O)—(CHR1)n—NH—, where n is 4-6 and each R1 is independently H or methyl, such that at most two R1's are methyl. In one embodiment, X is a 6-aminohexanoic acid residue.

According to the present invention, it is possible to provide a novel cell penetrating peptide that transports proteins into cells and / or into nuclei at higher frequency than conventional cell penetrating peptides, and a pharmaceutical containing the peptide.

The present invention relates to the identification and functional characterization of human cell-penetrating peptides (CPPs) and their use; in particular as transfection vehicles.

The present invention discloses cell penetrating peptides and conjugates of a cell penetrating peptide and a cargo molecule.

The invention provides cell penetrating peptide-nucleic acid conjugates having the formula P-L-N, wherein P is a cell penetrating peptide, N is a nucleic acid, preferably an oligonucleotide and more preferably a siRNA, and L is a hydrophilic polymer, preferably a polyethylene glycol (PEG)-based linker linking P and N together. Compositions, methods of use and methods for producing such conjugates are also disclosed.

The disclosure provides a cell penetrating peptide. The cell penetrating peptide includes an amino acid sequence of Dn, in which D represents an aspartate residue and 2≦n≦15.

The present invention provides a membrane-permeable complex for facilitating the delivery of a double-stranded ribonucleic acid molecule into a cell. Specifically, the invention provides a membrane-permeable complex that comprises a double-stranded ribonucleic acid molecule, such as a small interfering RNA, a cell-penetrating peptide, and a covalent bond linking the double-stranded ribonucleic acid to the cell-penetrating peptide. Also provided are methods of using the membrane-permeable complex of the present invention to deliver the double-stranded ribonucleic acid molecule to a cell or to inhibit expression of a gene product by a cell.

The invention relates to modification of a cell penetrating peptide for realizing a low-toxicity administration system with a positive targeting selecting function. A shielding peptide, an enzymolysis substrate peptide and a cell-penetrating peptide are connected in sequence, so that an activatable cell penetrating peptide is formed; and a medicament and / or a tracer and / or a medicament carrier is connected or embedded or adsorbed to the cell penetrating peptide, so that an administration system is constructed. According to a shielding peptide sequence, positive charges carried on the surface of the administration system can be reduced or completely neutralized, the cell penetrating capability of the cell penetrating peptide is shielded, and the toxicity of the administration system on normal cells of an organism is lowered; and an enzymolysis substrate peptide sequence can be identified by enzyme systems secreted specifically by different pathological change tissue cells and fractured by enzyme hydrolysis, so that a cell penetrating peptide is released and is used for carrying a medicament and / or a medicament carrier through a cell membrane, and the medicament enters cells and is brought into play. The invention aims to actively convey an antitumor medicament to tumor tissues in a targeted way and make the antitumor medicament enter tumor cells to a larger extent by using the administration system which can be used for activating a cell penetrating function, so that the toxicity at a non-tumor position is lowered while the antitumor effect of the medicament is enhanced.

A cell-penetrating peptide of (A) to (D) below gives cell membrane permeability and transmucosal absorbability to a physiologically active substance:(A) a peptide having the amino acid sequence of SEQ ID NO:1;(B) a peptide represented by SEQ ID NO:1 except that one or several basic amino acids are changed;(C) a peptide represented by SEQ ID NO:1 except that 1 to 5 amino acids are changed;(D) a peptide having: the reverse sequence of any of (A) to (C); an amino acid sequence which is the same as the reverse sequence of (A) except that one or several basic amino acids are changed; or an amino acid sequence which is the same as the reverse sequence of (A) except that 1 to 5 amino acids are changed.

The invention provides a method for knocking out a drug resistance gene mcr-1 through CRISPR-Cas9 in vitro and specialized cell penetrating peptide thereof. The method comprises the steps that a CRISPR-Cas9 system is constructed according to a target point sequence of an mcr-1 drug resistance gene sgRNA identification zone, a base sequence of the target point sequence is shown as SEQ NO.1, in the constructed CRISPR-Cas9 system, a T7 promoter is inserted into the portion in front of a start point of sgRNA transcription, a prokaryotic expression vector of Cas9 protein is constructed, regulation is conducted through the T7 promoter, the specialized cell penetrating peptide CPP2a is utilized for knocking out the mcr-1 drug resistance gene, a carrier pCas9-mcr is brought into a microbial cell, the microbial species can be gram negative bacteria, and the phenomenon that microbial mcr-a drug resistance gene is knocked out in vitro is achieved.

The present disclosure provides therapeutic agents for the treatment of age-related macular degeneration (AMD) and other eye disorders. One or more therapeutic agents can be used to treat any stages (including the early, intermediate and advance stages) of AMD, and any phenotypes of AMD, including geographic atrophy (including non-central GA and central GA) and neovascularization (including types 1, 2 and 3 NV). In some embodiments, the one or more therapeutic agents are or include an anti-dyslipidemic agent, an antioxidant, an anti-inflammatory agent, a complement inhibitor, a neuroprotector or an anti-angiogenic agent, or any combination thereof. In certain embodiments, the one or more therapeutic agents are or include an anti-dyslipidemic agent (e.g., an apolipoprotein mimetic or / and a statin). In some embodiments, the one or more therapeutic agents are mixed with, non-covalently associated with or covalently bonded to a cell-penetrating peptide (CPP), encapsulated in CPP-conjugated nanoparticles, micelles or liposomes, or modified (e.g., stapled, prenylated, lipidated or coupled to a small-molecule α-helix mimic) to acquire membrane-translocating ability. In certain embodiments, the one or more therapeutic agents are administered by eye drop.

The present invention relates to conjugates comprising a protein and multivalent cell-penetrating peptide(s), each multivalent cell-penetrating peptide comprising at least two cell-penetrating peptides, wherein the multivalent cell-penetrating peptide(s) is / are covalently attached to the protein. The present invention furthermore relates to a method of generating the conjugates and to their medical uses, in particular their use in the diagnosis, prevention and / or treatment of diseases. The present invention relates to methods of diagnosis, prevention and / or treatment of diseases, comprising administering the conjugates of the invention to a patient.

The invention belongs to the medicinal preparation field, relates to a cell-penetrating peptide modified nanoparticle, and concretely relates to a nanoparticle delivery system for oral polypeptide and protein medicines, and its preparation method. The medicine delivery system is composed of the nanoparticle, cell-penetrating peptides modified on the surface of the nanoparticle, and the polypeptide protein medicines sealed by the nanoparticle, wherein the average particle size range of the medicine delivery system is 10-500nm. The cell-penetrating peptide modified nanoparticle and glucosaminoglycan having electronegative cell surfaces undergo electric property attraction and then undergo endocytosis, so the cell-penetrating peptide modified nanoparticle and the glucosaminoglycan are integrally taken into cells; and the cell-penetrating peptide modified nanoparticle has an alimentary canal mucous membrane penetrating capability after the cell-penetrating peptide modified nanoparticle is orally taken, and can deliver the polypeptide protein medicines carried by the cell-penetrating peptide modified nanoparticle to the whole body for blood circulation, so the oral biological utilization degree of the medicines are improved. The cell-penetrating peptide modified nanoparticle has the advantages of improvement of the stability of polypeptide and protein medicines in the alimentary canal, reduction of the application amount of cell-penetrating peptides, and reduction of possible toxic side effects caused by the cell-penetrating peptides.

The invention belongs to a liposome, in particular relates to a compound liposome preparation with high targeting property of tumor tissues and efficient penetrability of tumor cells. The invention is characterized in that hyaluronic acid or sodium hyaluronate, tumor cell selective penetrating peptides and a liposome are used for together constructing a compound liposome. The compound liposome is characterized by utilizing the dual-tumor cell targeting property of the hyaluronic acid and tumor cell selective penetrating peptides to effectively solve the problem that because a conventional liposome and traditional cell penetrating peptides have no selectivity on normal cells and tumor cells, the toxicity is increased when the drug effect is increased in the therapeutic process, thereby fully meeting the clinical requirements of high efficiency and low toxicity when anti-tumor drugs are prepared into preparations for treating diseases.

The invention relates to the biotechnical field, and concretely relates to a tumor cell targeting penetrating peptide, a polynucleotide molecule and a use thereof, and a targeting drug delivery system containing the tumor cell targeting penetrating peptide. The tumor cell targeting penetrating peptide is characterized in that the tumor cell targeting penetrating peptide contains a CPPs structure domain having cell penetrating peptide activity and an EFG third ring sample mimic peptide structure domain with specific targeting affinity to tumor cells. The tumor cell targeting penetrating peptide has a substantial cell penetrating effect, has the novel characteristics of cell specificity and species specificity, and can be used to diagnose tumor diseases and develop medicines required in the treatment process.

Vaccines that comprise or generate immunomodulatory flagellin polypeptides able to stimulate an innate immune response intracellularly and extracellularly employ viruses, bacteria or parasitic cells that contain expression systems for such polypeptides, as well as fusion proteins that contain antigens and / or cell penetrating peptides along with the immunomodulatory peptide.

The present invention relates to a conjugate of cell penetrating peptide and an active ingredient; and its use. Specifically, a conjugate including a cell penetrating peptide which is a peptide comprising amino acid sequence of SEQ ID NO:1, a fragment of any one sequence of SEQ ID NO:1, or a peptide having above 80% homology with the above-mentioned sequence; and a composition comprising the same are disclosed.

The invention provides compositions useful as molecular probes. In particular, the invention provides activatable cell penetrating peptides comprising a fluorescence donor and a fluorescence acceptor. Exemplary fluorescence donors and fluorescence acceptors include compounds derived from cyanine. Also provided are ratiometric, multispectral, and excitation lifetime imaging methods for detecting the molecular probes provided herein.

The present invention relates to a conjugate of cell penetrating peptide and an active ingredient; and its use. Specifically, a conjugate including a cell penetrating peptide which is a peptide comprising any one amino acid sequence of SEQ ID NO: 1 to SEQ ID NO: 6, a fragment of any one sequence of SEQ ID NO: 1 to SEQ ID NO: 6, or a peptide having above 80% homology with the above-mentioned sequence; and a composition comprising the same are disclosed.

The invention provides a novel polypeptide modified tumor targeted liposome of a targeted integrin receptor. The novel polypeptide is mainly formed by covalent linkage of ring-shaped RGD and cell penetrating peptides, and not only has the selective targeting capability of an integrin receptor, but also can achieve mediated endocytosis; the liposome mainly comprises phospholipid, cholesterol, lipid-polyethyleneglycol and lipid-polyethyleneglycol-novel polypeptide ligand chimeric substance, and is a very potential tumor targeted treatment carrier.

The present invention provides a method of determining or identifying or isolating a cell-penetrating peptide (CPP) or analog or derivative thereof having cell-type selectivity and / or at least capable of passing through a Blood Brain Barrier of an animal subject. This invention also provides CPPs and analogs and derivatives thereof, such as those set forth in SEQ ID NOs: 1-27 of the Sequence Listing, and compositions comprising one or more of the CPPs, including conjugates in which a CPP or analog or derivative thereof is linked to a cargo molecule. The invention also provides methods for transporting cargo molecules across cell membranes to specific locations within cells, and for treating, preventing and / or diagnosing diseases that are treatable by a cargo molecule to which a CPP or analog or derivative of the invention is attached. The invention also provides tailored peptide libraries for use in identifying or isolating CPPs.

The invention discloses a preparation method of double-targeting cationic ultrasound microbubbles carrying cell-penetrating peptide iRGD and belongs to the field of fundamental research. The preparation method uses materials, including DSPC, DSPE-PEG2000-maleimide, DSPE-PEG2000-Biotin, iRGD peptide, CCR2 antibody, stearic acid, branched-chain polyetherimide-600, N, N'-carbonyldiimidazole, and avidin; by bonding integrin Alpha v Beta3 targeting cell-penetrating peptide iRGD and the CCR2 antibody to surfaces of the microbubbles, double-targeting cationic ultrasonic contrast agent is constructed and has the double functions of carrying plasmid DNA and targeting tumor cells; combining ultrasound-mediated biological effect and iRGD cell-penetrating action, the agent is capable of promoting entry of genes into the tumor cells and improving gene transfection efficiency and is expected to be developed and applied to visual ultrasound-controlled-release genetic treatment of tumors.

The invention generally relates to synthetic mimics of cell penetrating peptides. More particularly, the invention relates to certain novel monomers, oligomers and polymers (e.g., co-polymers) that are useful for the preparation of synthetic mimics of cell penetrating peptides, their compositions, preparations and use.

The present invention relates to a fusion peptide wherein a self cell-penetrating Tat peptide having a self penetrating signal is bound to a human parathyroid hormone-derived peptide, a preparation thereof, and a skin slimming cosmetic composition comprising the same. Since the fusion peptide wherein the Tat peptide is bound to the human parathyroid hormone-derived peptide has high stability and superior skin absorption, the present invention provides a skin slimming agent having superior lipolysis effects and improved durability of the effects.

Elastin-like polypeptide (ELP) serves as a vector for thermally-targeted delivery of therapeutics, including cytotoxic chemotherapeutic drugs such as doxorubicin. Examples of an ELP-based delivery vehicle can comprise: (1) a cell penetrating peptide, such as a Tat protein, (2) ELP, and (3) the lysosomally degradable glycylphenylalanylleucylglycine (GFLG) spacer and a cysteine residue conjugated to therapeutic such as doxorubicin, or a analog thereof.

The present invention relates to a conjugate of cell penetrating peptide and an active ingredient; and its use. Specifically, a conjugate including a cell penetrating peptide which is a peptide comprising any one amino acid sequence of SEQ ID NO: 1 to SEQ ID NO: 156, a fragment of any one sequence of SEQ ID NO: 1 to SEQ ID NO: 156, or a peptide having above 80% homology with the above-mentioned sequence; and a composition comprising the same are disclosed.