Lung-specific targeting-peptide (LTP), compositions, and uses thereof
View Patent ↗Disclosed is a synthetic, non-naturally occurring 12-amino acid peptide, Lung-specific Targeting Peptide, belonging to the larger class of cell penetrating peptides, for delivery of both diagnostic and potentially therapeutic agents to the lung. Also disclosed are methods of treating pulmonary disease, e.g., chronic obstructive pulmonary disease (COPD), emphysema, chronic bronchitis, asthma, primary ciliary dyskinesia (PCD), cystic fibrosis (CF), and lung cancer.
1 . A method of introducing a cargo into a lung epithelial cell, comprising administering to the lung epithelial cell a formulation comprising an effective amount of a Lung-specific Targeting-Peptide (LTP) connected to the cargo, wherein the LTP comprises the amino acid sequence of SEQ ID NO: 1 or 2, the formulation is effective to introduce the cargo to the lung epithelial cell, and the cargo is a drug or therapeutic, nanoparticle, peptide, protein, nucleic acid, or detectable agent.
2 . A formulation comprising a Lung-specific Targeting-Peptide (LTP) connected to a drug or therapeutic, nanoparticle, peptide, protein, nucleic acid, or detectable agent, and a pharmaceutically acceptable carrier, wherein the LTP comprises the amino acid sequence of SEQ ID NO: 1 or 2.
3 . The formulation of claim 2 , wherein the LTP is further connected to a label at the N- and/or the C-termini.
4 . The formulation of claim 2 , wherein the LTP is further connected to a label at the C-terminus.
5 . The formulation of claim 2 , wherein the LTP is conjugated to the drug or therapeutic, the nanoparticle, the peptide, the protein, the nucleic acid, or the detectable agent via an ester linkage, disulfide or protease sensitive linkers.
6 . The formulation of claim 2 , wherein the LTP is connected to a nucleic acid for gene therapy, a small interfering RNA (siRNA), a small nuclear RNA (snRNA), a non-coding RNA, a microRNA (miRNA), a messenger RNA (mRNA), a catalytic RNA, a catalytic DNA, an antisense RNAo, a nucleoside analog, a polynucleic acid decoy, an aptamer, a plasmid, or a nucleic acid vector.
7 . The formulation of claim 2 , wherein the LTP is a linear peptide.
8 . The formulation of claim 2 , formulated as a sustained-delivery formulation.
9 . The formulation of claim 2 , wherein the formulation uses a controlled release system.
10 . The formulation of claim 2 , wherein the formulation uses a slow release system.
11 . A method of treating a human subject suffering from a lung disease or disorder, the method comprising administering the formulation of claim 2 to the human subject, wherein the formulation is administered in an amount effective to treat the lung disease or disorder.
12 . A method of growing and/or re-cilliating tracheal epithelial cells (MTCs) and/or nasal epithelial cells of a mammal, the method comprising administering an effective amount of the formulation of claim 2 to the mammal, wherein the formulation is effective to grow and/or re-cilliate MTCs and/or nasal epithelial cells of a mammal.
13 . A cyclic peptide comprising the amino acid sequence of SEQ ID NOs: 1 or 2, wherein an N-terminal lysine is added to the amino acid sequence, wherein the N-terminal lysine connects to the C-terminus of the amino acid sequence, and wherein the cyclic peptide is connected to a nucleic acid.
14 . A formulation comprising a Lung-specific Targeting-Peptide (LTP) connected to a nucleic acid and a pharmaceutically acceptable carrier, wherein the LTP is cyclic and comprises the amino acid sequence of SEQ ID NO: 1 or 2.