EP4713351A1 - Therapeutic pdgf-a molecules - Google Patents

Abstract

The present invention relates to peptide ligands that bind to an extracellular or transmembrane region of PDGFR-alpha. The invention also relates to compositions comprising the peptide ligands and methods of using the same.

Description

Therapeutic molecules Field of invention The present invention relates to peptide ligands that may bind to an extracellular or transmembrane region of PDGFR-alpha. The invention more particularly relates to peptide ligands that may be conjugated to another moiety for use as a drug conjugate. Background One challenge in drug development is the specific in vivo delivery in the target tissue/cells. This is particularly crucial for drugs with limited in vivo bioavailability and potential for off-target side effects, such as anti-cancer drug and nucleic acid drugs. Various targeted-drug delivery strategies have since been developed. One of the most successful targeted-drug delivery is the use of trimeric N-acetyl galactosamine (GalNAc) ligand which binds to the asialoglycoprotein receptor (ASPGR), highly expressed on hepatocytes. This technology has shown great success in liver/hepatocyte-specific delivery. Conjugating GalNAc with antisense oligonucleotides (ASOs) or small interfering RNA (siRNA) can dramatically increase the uptake of the RNA oligos by hepatocytes, reduce the therapeutic dosage, and prolong their effect. This conjugation technology has led to the approval of givosiran (Givlaari^®) for the treatment of acute hepatic porphyria, and a long list of other GalNAc-ASO or GalNAc-siRNA conjugates in the clinical development pipeline. Based on the strong demand of a fibroblast targeted RNA or DNA oligonucleotide delivery strategy for conditions where muscle interstitial fibroblasts (MIFs) are the therapeutic targets, including congenital muscular dystrophies, the inventors identified ligand peptide sequences capable of binding to a cell surface protein that is predominantly expressed in MIFs. The present invention is aimed at addressing this need. The inventors have identified a 125 amino acid sequence within PDGFA as the primary PDGFR-alpha binding region that can be conjugated to an additional moiety such as antisense oligonucleotides (ASO), small interfering RNA (siRNA) or small activating RNA (saRNA). Internalization/uptake of these conjugated peptides by PDGFR-alpha expressing cells such as MIFs results in the targeted delivery of the therapeutic agent to these cells. Summary of the invention We provide peptide ligands that may bind to an extracellular or transmembrane region of PDGFR-alpha for use as a drug conjugate. According to a first aspect of the present invention, there is provided a peptide ligand that binds to an extracellular or transmembrane region of PDGFR-alpha, wherein the peptide ligand comprises SEQ ID NO: 2 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 3 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 4 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 5 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 6 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprising SEQ ID NO: 7 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 8 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 9 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 10 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 11 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 12 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 13 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 14 or a peptide ligand sequence having at least 80% homology thereto. In one embodiment, the N-terminus and/or C-terminus of the peptide ligand may comprise at least one positively charged residue. In one embodiment, the peptide ligand may comprise the amino acid sequence of SEQ ID NO:1, or an amino acid sequence with at least 80% homology thereto. In one embodiment, the extracellular or transmembrane region of PDGFR-alpha may be expressed by fibroblasts. In one embodiment the peptide ligand may bind podocytes, and/or cells originating from tissues selected from list of liver, kidney, neural and/or endothelium. In one embodiment, the peptide ligand may be internalised upon binding to the extracellular or transmembrane region of PDGFR-alpha. In one embodiment, the peptide ligand may further comprise an additional moiety. In another embodiment, the additional moiety may be selected from a toxin, enzyme, radioisotope, half- life extending moiety, label, therapeutic molecule or other chemical moiety. In another embodiment, the therapeutic molecule may be an RNA or DNA oligonucleotide. In another embodiment, the RNA or DNA oligonucleotide may be an ASO, siRNA or saRNA. According to a second aspect of the present invention, there is provided a pharmaceutical composition comprising a peptide ligand according to the invention and optionally a pharmaceutically acceptable carrier. According to a third aspect of the present invention, there is provided a method for treating a cancer, an immune disorder, a respiratory disorder, metabolic disorder, inflammatory disorder, allergy, transplant rejection, viral infection, muscular dystrophy and/or neuromuscular disease, immune deficiency, and other immune system-related disorder comprising administering a therapeutically effective amount of a peptide ligand according to the invention or a pharmaceutical composition according to the invention. In one embodiment the muscular dystrophy may be selected from a congenital muscular dystrophy or myopathy, Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, tibial muscular dystrophy, distal muscular dystrophy, and Emery-Dreifuss muscular dystrophy. In another embodiment the muscular dystrophy and/or neuromuscular disease may be a congenital muscular dystrophy or myopathy resulting from mutations in any of the three collagen VI genes (Col6A1, Col6A2, Col6A3), clinically known as Ullrich congenital muscular dystrophy or the milder Bethlem myopathy and intermediate clinical manifestations. In another embodiment fibrosis may be targeted in the muscular dystrophy and/or neuromuscular disease selected from a congenital muscular dystrophy or myopathy, Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, tibial muscular dystrophy, distal muscular dystrophy, and Emery-Dreifuss muscular dystrophy. In another embodiment the cancer may be selected from bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, kidney cancer, sarcoma of soft tissue, cancer of the urethra, cancer of the bladder, renal cancer, lung cancer, non-small cell lung cancer, thymoma, urothelial carcinoma leukemia, prostate cancer, mesothelioma, adrenocortical carcinoma, lymphomas, such as such as Hodgkin's disease, non-Hodgkin's, gastric cancer, and multiple myelomas. According to a fourth aspect of the present invention, there is provided a use of a peptide ligand according to the invention or a pharmaceutical composition according to the invention in the manufacture of a medicament for the treatment of a cancer, an immune disorder, a respiratory disorder, metabolic disorder, inflammatory disorder, allergy, transplant rejection, viral infection, muscular dystrophy, immune deficiency, and other immune system-related disorder comprising administering a therapeutically effective amount of a peptide ligand according to the invention or a pharmaceutical composition according to the invention. In one embodiment the muscular dystrophy and/or neuromuscular disease may be selected from a congenital muscular dystrophy or myopathy, Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, tibial muscular dystrophy, distal muscular dystrophy, and Emery-Dreifuss muscular dystrophy. In another embodiment the muscular dystrophy and/or neuromuscular disease may be a congenital muscular dystrophy or myopathy resulting from mutations in any of the three collagen VI genes (COL6A1, COL6A2, COL6A3), clinically known as Ullrich congenital muscular dystrophy or Bethlem myopathy and intermediate clinical manifestations. In another embodiment fibrosis may be targeted in the muscular dystrophy selected from a congenital muscular dystrophy or myopathy, Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, tibial muscular dystrophy, distal muscular dystrophy, and Emery-Dreifuss muscular dystrophy. In another embodiment the cancer may be selected from bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, kidney cancer, sarcoma of soft tissue, cancer of the urethra, cancer of the bladder, renal cancer, lung cancer, non-small cell lung cancer, thymoma, urothelial carcinoma leukemia, prostate cancer, mesothelioma, adrenocortical carcinoma, lymphomas, such as such as Hodgkin's disease, non-Hodgkin's, gastric cancer, and multiple myelomas. According to a fifth aspect of the present invention, there is provided a peptide ligand according to the invention or a pharmaceutical composition according to the invention for use as a treatment. According to a sixth aspect of the present invention, there is provided a peptide ligand according to the invention or a pharmaceutical composition according to the invention for use as a treatment for a cancer, an immune disorder, a respiratory disorder, metabolic disorder, neurological disease, inflammatory disorder, allergy, transplant rejection, viral infection, muscular dystrophy, immune deficiency, and other immune system-related disorder comprising administering a therapeutically effective amount of a peptide ligand according to the invention or a pharmaceutical composition according to the invention. In one embodiment the muscular dystrophy and/or neuromuscular disease may be selected from a congenital muscular dystrophy or myopathy, Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, tibial muscular dystrophy, distal muscular dystrophy, and Emery-Dreifuss muscular dystrophy. In another embodiment the muscular dystrophy may be a congenital muscular dystrophy or myopathy resulting from mutations in any of the three collagen VI genes (COL6A1, COL6A2, COL6A3), clinically known as Ullrich congenital muscular dystrophy or Bethlem myopathy and intermediate clinical manifestations. In another embodiment fibrosis may be targeted in the muscular dystrophy and/or neuromuscular disease selected from a congenital muscular dystrophy or myopathy, Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, tibial muscular dystrophy, distal muscular dystrophy, and Emery-Dreifuss muscular dystrophy. In another embodiment the cancer may be selected from bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, kidney cancer, sarcoma of soft tissue, cancer of the urethra, cancer of the bladder, renal cancer, lung cancer, non-small cell lung cancer, thymoma, urothelial carcinoma leukemia, prostate cancer, mesothelioma, adrenocortical carcinoma, lymphomas, such as such as Hodgkin's disease, non-Hodgkin's, gastric cancer, and multiple myelomas. According to a seventh aspect of the present invention, there is provided a nucleic acid molecule comprising a nucleotide sequence encoding a peptide ligand according to the invention. In one embodiment the nucleic acid molecule may comprise a nucleotide sequence encoding a peptide ligand according to the invention selected from SEQ ID NO: 15 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 16 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 17 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 18 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 19 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 20 or a nucleotide having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 21 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 22 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 23 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 24 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 25 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 26 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 27 or a nucleotide sequence having at least 80% homology thereto. In one embodiment, the N-terminus and/or C-terminus additionally comprises nucleotides encoding at least one positively charged residue. According to an eighth aspect of the present invention, there is provided a vector according to the invention. According to a ninth aspect of the present invention, there is provided a host cell comprising a nucleic acid according to the invention or a vector according to the invention. In one embodiment the host cell may be a bacterial, yeast, insect, plant, viral or mammalian cell. According to a tenth aspect of the present invention, there is provided a method for producing the peptide ligand of the invention comprising a nucleic acid encoding said peptide ligand in a host cell and isolating the peptide ligand from the host cell. According to an eleventh aspect of the present invention, there is provided a system to identify peptide ligand sequences which can specifically bind to PDGFR-alpha for drug delivery, comprising the steps of identifying a cell-surface epitope, design of peptide ligand sequence capable of binding at the PDGF-A-PDGFR-alpha interface, and uptake and/or internalisation of the peptide ligand by the host cell. According to a twelfth aspect of the present invention, there is provided a multimeric binding complex comprising at least two of the peptide ligands according to the invention. In one embodiment the multimeric binding complex may comprise an additional moiety. In another embodiment the additional moiety may be selected from a toxin, enzyme, radioisotope, half- life extending moiety, label, therapeutic molecule or other chemical moiety. In another embodiment the therapeutic molecule is an RNA or DNA oligonucleotide. In another embodiment the RNA or DNA oligonucleotide is an ASO, siRNA or saRNA. According to a thirteenth aspect of the present invention, there is provided a tissue delivery complex which comprises a peptide ligand according to the invention or a multimeric binding complex according to the invention. In one embodiment the tissue delivery complex may be a muscle tissue delivery complex. In another embodiment the tissue delivery complex may be a liver, kidney and/or endothelium delivery complex. In another embodiment the tissue delivery complex according to the invention may be for the use in the treatment of muscular dystrophy and/or neuromuscular disease, and/or diseases of the liver, kidney and/or endothelium. In another embodiment the muscular dystrophy and/or neuromuscular disease may be a congenital muscular dystrophy or myopathy, Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, tibial muscular dystrophy, distal muscular dystrophy, and Emery-Dreifuss muscular dystrophy. In another embodiment fibrosis may be targeted in the muscular dystrophy and/or neuromuscular disease selected from a congenital muscular dystrophy or myopathy, Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, tibial muscular dystrophy, distal muscular dystrophy, and Emery-Dreifuss muscular dystrophy. In another embodiment the muscular dystrophy and/or neuromuscular disease may be a congenital muscular dystrophy or myopathy resulting from mutations in any of the three collagen VI genes (COL6A1, COL6A2, COL6A3), clinically known as Ullrich congenital muscular dystrophy or Bethlem myopathy and intermediate clinical manifestations. According to a fourteenth aspect of the present invention, there is provided a method of modifying the expression of a target gene in a fibroblast comprising providing to the cell an RNA or DNA oligonucleotide conjugated to a peptide ligand according to the invention. In one embodiment, the RNA or DNA oligonucleotide may be an ASO, siRNA or saRNA. According to a fifteenth aspect of the present invention, there is provided a kit comprising a peptide ligand according to the invention or a pharmaceutical composition according to the invention and optionally instructions for use. According to a sixteenth aspect of the present invention, there is provided a therapeutic molecule comprising a peptide ligand according to the invention. In one embodiment the therapeutic molecule may be an RNA or DNA oligonucleotide. In one embodiment the RNA or DNA oligonucleotide may be an ASO, siRNA or saRNA. According to a seventeenth aspect of the present invention, there is provided a method of delivering to a fibroblast and/or podocyte and/or cells originating from tissues selected from list of liver, kidney, skeletal muscle and/or endothelium a peptide ligand according to the invention, the pharmaceutical composition according to the invention, or the therapeutic molecule according to the invention. According to a nineteenth aspect of the present invention, there is provided a method of screening for a peptide ligand according to the invention. In one embodiment the method may comprise analysing a first single-cell RNA sequencing dataset of a first cell population to identify genes encoding cell surface proteins from the first cell population and/or analysing a surfaceome dataset of said first cell population to identify cell-surface proteins from the first cell population, comparing the first single-cell RNA sequencing and/or surfaceome dataset(s) to a second dataset, and excluding the cell surface proteins highly expressed in liver and/or kidneys. In one embodiment the method may comprise the identification of a target that is specifically or more abundantly expressed in the first cell population. According to a twentieth aspect of the present invention, there is provided a method for targeting fibroblasts comprising administering a peptide ligand according to the invention or a pharmaceutical composition according to the invention, wherein the peptide ligand targets an extracellular or transmembrane region of PDGFR-alpha. According to a twenty-first aspect of the present invention, there is provided a method for targeting podocytes and/or cells originating from tissues selected from list of liver, kidney, skeletal muscle and/or endothelium comprising administering a peptide ligand according to the invention or a pharmaceutical composition according to the invention. The invention is described in the following non-limiting figures and tables. Brief Description of the Figures Figure 1. Flow chart illustrating the identification of top 20 genes encoding for cell-surface protein in MIFs. Preliminary data was generated by using scRNA-seq public dataset deposited in Human Cell Landscape (HCL: http://bis.zju.edu.cn/HCL/). Specifically, scRNA- seq data from an adult muscle and a foetal muscle are available on the HCL website. The first step has been the identification of MIFs population among the other cell populations present in skeletal muscle. The cellular localization of the proteins encoded by 600 genes expressed in MIFs was analysed by ingenuity pathway analysis (IPA).64 genes were identified encoding for plasma membrane proteins. We then excluded those highly expressed in liver and kidneys to reduce ASO accumulation in these two organs. This eventually led to the identification of 20 genes encoding for cell-surface proteins expressed specifically or abundantly in MIFs. Figure 2. Characterization of the target receptor. (A) Immunofluorescence staining of the subunit of a PDGFRα receptor(in green), desmin (in red, marker of myogenic cells) and nuclei (in blue) in mixed cell populations from a control muscle biopsy. (B) Immunofluorescence staining of the PDGFRα receptor (in green), laminin (in red, marker of myofiber membrane), CD31 (in grey, marker of endothelium) and nuclei (in blue) in muscle biopsy from control and patient with COL6-CMD. (C) Real-time PCR analysis of the transcripts of the receptor protein in skin fibroblasts from healthy controls (n=5), patients with COL6-CMD (n=19), HepG2 cell line (graph on the top), MIFs and myoblasts cultured from control skeletal muscle biopsy (graph on the bottom left), and from frozen skeletal muscle tissues (control n=2, patients n=3) (graph on bottom right). (D) 3D structure of the subunit of the PDGFRα. Two binding domains are identified. Pocket 1 is an allosteric pocket close to the transmembrane domain. Pocket 2 is the binding domain of the natural ligands. Figure 3. Peptides screening. Cultured cells were treated with 13 FAM-labelled peptides at 10 µM for 3 hours, then fixed and visualized under fluorescence microscopy. Eight cell lines were tested, including human fibroblasts (Hum Fibroblast), mouse fibroblasts (Ms Fibroblast), human hepatocytes (HepG2), human endothelial cells (HUVEC), mouse myoblasts (Ms Myoblast), human kidney proximal tubular cell (HK2), human podocyte (Hum podocyte) and mouse podocyte (Ms Podocyte). Peptides showing positive signals in cells were indicated by framed in red. Figure 4. Human (Hum fibroblast) and mouse fibroblasts (Ms fibroblast) were treated with peptide 3 at 10 µM for a range of time points between 5 minutes to 3 hours. Cells were then fixed and visualized under fluorescence microscopy. Peptides showing positive signals in cells were indicated by framed in red. Figure 5: 10 µM of each FAM-peptide have been tested in human (A) and mouse (B) cell lines. After 3h incubation, samples were fixed with 4% PFA and visualized under fluorescence microscope at 40x magnification. FAM-peptides are shown in green and nuclei in blue. (C) Semi-quantification based on the mean intensity of each peptide normalized to number of nuclei. (D) Semi-quantification based on mean area covered by each peptide normalized to number of nuclei. Figure 6: FAM-peptide 3 (A) and FAM-peptide 5 (B) were in human primary fibroblasts and mouse fibroblasts (3T3). After peptide’s incubation, samples were fixed with 4% PFA and visualized under fluorescence microscope at 40x magnification. FAM-peptides are shown in green and nuclei in blue. The semi-quantification based on the mean intensity normalized to number of nuclei is shown for FAM-Peptide 3 (C) and FAM-Peptide 5 (D). Figure 7: (A) (i) Z-stack of images of FAM-peptide 3 and FAM-peptide 5 captured by confocal microscopy using 40x magnification. FAM-peptides are shown in green and nuclei in blue. (ii) Time lapse images of Cy5.5-peptide 3 and Cy5.5-peptide 5 acquired with Nikon ECLIPSE Ti Live cell imaging. Images were acquired every 30 sec for 15min and every 1min for 3h. Cy5.5- peptides are shown in red and nuclei in blue. Scale bar: 100 µm. (B) RT-qPCR was performed in RNA samples collected from human fibroblasts treated for 72h with PDGFRα-siRNA (hs.RiPDGFRA.13.1). Data were normalized to untreated samples and analyzed by one-way ANOVA and post-Bonferroni test. Data are presented as mean ± SD (∗p ≤ 0.05; ∗∗p ≤ 0.01; ∗∗∗p ≤ 0.001). (ii) Cy5.5-peptide 3 and FAM-peptide 5 were incubated for 1h with untreated human fibroblasts and fibroblasts treated with PDGFRα-siRNA for 72h. Peptide 3 is shown in red, peptide 5 in green and nuclei in blue. Scale bars: 100 µm. Figure 8: 10 µM of peptide 3 (A), peptide 5 (B), peptide 13 (C) and peptide 3(S) were incubated for 3h with primary fibroblasts followed by 30 min incubation with LysoBrite. Cells were then fixed with 4% PFA visualized under fluorescence microscope. Peptide 3, 5 and 3(S) labelled with Cy5 are shown in red, LysoBrite in green in image A, B and D, and Peptide 13 labelled with FAM in green and LysoBrite in red in image C while nuclei in blue. Scale bars: 50 µm and 100 µm. Figure 9: RT-qPCR was performed in human fibroblasts treated with Pep3(C>S)-MOE-5/6 and MOE-5/6 in gymnotic delivery (A) and using lipofectamine 2000 (L2K) as transfection reagent (B). Data are shown as mutant/wild type ratio and were analyzed using one-way ANOVA and post-Bonferroni test. Data are presented as mean ± SD (∗p ≤ 0.05; ∗∗p ≤ 0.01; ∗∗∗p ≤ 0.001). (C) 10 µM of peptide 3(S) was incubated for 3h with primary fibroblasts followed by 30 min incubation with LysoBrite. Cells were than fixed with PFA 4% and visualized under fluorescence microscope. Cy5.5-peptides are shown in red, LysoBrite in green and nuclei in blue. Scale bars: 100 µm. (D) Gel electrophoresis of PCR products performed in RNA samples isolated from patient’s skin fibroblasts untreated and treated with Pep3(C>S)-MOE-5/6, Pep3(+R)-MOE5/6 and MOE-5/6 in gymnotic delivery using 100 nM of ASOs concentration. The top band represents the mutant transcript with the inclusion of the pseudo exon and the bottom band the wildtype transcripts. (E) RT-qPCR was performed in human fibroblasts treated with Pep3(C>S)-MOE-5/6, Pep3(+R)-MOE and MOE-5/6 in gymnotic delivery. Data are shown as mutant/wild type ratio and were analyzed using one-way ANOVA and post-Bonferroni test. Data are presented as mean ± SD (∗p ≤ 0.05; ∗∗p ≤ 0.01; ∗∗∗p ≤ 0.001). Figure 10: (A) RT-qPCR was performed in human fibroblasts treated with PMO9, Pep3-PMO9, and Pep5-PMO9 in gymnotic delivery at 200nM and 500nM. Data are shown as mutant/wild type ratio and were analyzed using one-way ANOVA and post-Bonferroni test. Data are presented as mean ± SD (∗p ≤ 0.05; ∗∗p ≤ 0.01; ∗∗∗p ≤ 0.001). (B) Gel electrophoresis of PCR products amplified from RNA samples isolated from patient’s skin fibroblasts untreated (NT) and treated with PMO9, Pep3-PMO9, and Pep5-PMO9 in gymnotic delivery at 200nM and 500nM. The top band represents the mutant transcripts with the inclusion of the pseudo exon and the bottom band represents the wild type transcripts. (C) Cytotoxicity assay performed in UCMD fibroblasts after 1 day and 4 days treatment with compounds in gymnotic delivery. Figure 11: Schematic representation of the endosome-lysosome pathway. Detailed description The present disclosure will now be further described. In the following passages, different aspects of the disclosure are defined in more detail. Each aspect so defined may be combined with any other aspect or aspects unless clearly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or features indicated as being preferred or advantageous. Generally, nomenclatures used in connection with, and techniques of, cell and tissue culture, pathology, oncology, molecular biology, immunology, microbiology, genetics and protein and nucleic acid chemistry and hybridization described herein are those well-known and commonly used in the art. The methods and techniques of the present disclosure are generally performed according to conventional methods well-known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification unless otherwise indicated. See, e.g., Green and Sambrook et al., Molecular Cloning: A Laboratory Manual, 4th ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (2012); Therapeutic Monoclonal Antibodies: From Bench to Clinic, Zhiqiang An (Editor), Wiley, (2009); and Antibody Engineering, 2nd Ed., Vols. 1 and 2, Ontermann and Duebel, eds., Springer-Verlag, Heidelberg (2010). Enzymatic reactions and purification techniques are performed according to manufacturer's specifications, as commonly accomplished in the art or as described herein. The nomenclatures used in connection with, and the laboratory procedures and techniques of, analytical chemistry, synthetic organic chemistry, and medicinal and pharmaceutical chemistry described herein are those well-known and commonly used in the art. Standard techniques are used for chemical syntheses, chemical analyses, pharmaceutical preparation, formulation, and delivery, and treatment of patients. As used herein, the term "homology" generally refers to the percentage of amino acid residues in a sequence that are identical with the residues of the reference polypeptide with which it is compared, after aligning the sequences and in some embodiments after introducing gaps, if necessary, to achieve the maximum percent homology, and not considering any conservative substitutions as part of the sequence identity. Thus, the percent homology between two amino acid sequences is equivalent to the percent identity between the two sequences. Neither N- or C-terminal extensions, tags or insertions shall be construed as reducing identity or homology. Methods and computer programs for the alignment are well known. The percent identity between two amino acid sequences can be determined using well known mathematical algorithms. As used herein, “peptide ligand” means a peptide capable of interacting with a cell-surface receptor or a cell-surface moiety. In certain embodiments, a peptide ligand is capable of binding the cell-surface receptor or the cell-surface moiety. In another embodiment, a peptide ligand is capable of being internalized when it interacts with or binds the cell-surface receptor or the cell-surface moiety. In another embodiment, the peptide ligand is not an antibody or fragment thereof. In another embodiment, the peptide ligand is an antibody or fragment thereof. According to a first aspect of the present invention, there is provided a peptide ligand that binds to an extracellular or transmembrane region of PDGFR-alpha, wherein the peptide ligand comprises SEQ ID NO: 2 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 3 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 4 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 5 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 6 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprising SEQ ID NO: 7 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 8 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 9 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 10 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 11 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 12 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 13 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 14 or a peptide ligand sequence having at least 80% homology thereto. In one embodiment the sequence homology is at least 60%, 65%, 70%, 75%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%. In one embodiment, the peptide ligand comprises SEQ ID NO: 33. In one embodiment, the peptide ligand comprises SEQ ID NO: 34. In some embodiments, there is provided a peptide ligand that is a variant of any of the above peptide ligands shown in Table 3 and having one or more amino acid substitutions, deletions, insertions or other modifications, and which retains a biological function of the peptide ligand, that is binding to an extracellular or transmembrane region of PDGFR-alpha. Thus, variant peptide ligand can be sequence engineered. Modifications may include one or more substitution, deletion or insertion of one or more codons encoding the peptide ligand that results in a change in the amino acid sequence as compared with the native sequence peptide ligand. Amino acid substitutions can be the result of replacing one amino acid with another amino acid having similar structural and/or chemical properties, such as the replacement of a leucine with a serine, i.e., conservative amino acid replacements. Insertions or deletions may optionally be in the range of about 1 to 5, for example 1, 2, 3, 4, or 5 amino acids. The variation allowed may be determined by systematically making insertions, deletions or substitutions of amino acids in the sequence and testing the resulting variants for activity exhibited by the full- length or mature native sequence. A variant may include a truncated versions of the peptide ligand which retains a biological function of the peptide ligand. In one embodiment, the N-terminus and/or C-terminus of the peptide ligand may comprise at least one positively charged residue. In one embodiment, the N-terminus of the peptide ligand may comprise at least one arginine, lysine and/or histidine residues. In one embodiment, the N-terminus and/or C-terminus of the peptide ligand may comprise additionally comprise X positively charged residues, wherein X is 1 to 8. In one embodiment, the N-terminus and/or C- terminus of the peptide ligand may comprise additionally comprise X arginine, lysine and/or histidine residues, wherein X is 1 to 8. For example, the N-terminus and/or C-terminus of the peptide ligand may comprise additionally comprise 1 positively charged residue, for example arginine, lysine or histidine; 2 positively charged residues, for example arginine, lysine and/or histidine residues; 3 positively charged residues, for example 3 arginine, lysine and/or histidine residues; 4 positively charged residues, for example 4 arginine, lysine and/or histidine residues; or 5 positively charged residues, for example 5 arginine, lysine and/or histidine residues; or 6 positively charged residues, for example 6 arginine, lysine and/or histidine residues; or 7 positively charged residues, for example 7 arginine, lysine and/or histidine residues; or 8 positively charged residues, for example 8 arginine, lysine and/or histidine residues. The addition of positively charged residues to the N-terminus and/or C-terminus of the peptide ligand reduces endosomal entrapment and promotes endosomal escape. Endosomal entrapment and lysosomal degradation are well-known challenges for ASOs and peptides. Studies have shown that only around 1% of ASOs are able to efficiently escape from the endosomes, and for peptides, the endo-lysosomal route often leads to complete degradation, hindering their proper subcellular localization and bioavailability. Peptides can achieve endosomal escape through the presence of positively charged amino acids or amino acids that can acquire positive charges within acidic environments like endosomes. In one embodiment, the peptide ligand may comprise the amino acid sequence of SEQ ID NO:1, or an amino acid sequence with at least 80% homology thereto. In one embodiment the sequence homology is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%. In one embodiment, the peptide ligand binds the ligand binding region of PDGFR-alpha. In one embodiment, the peptide ligand binds the whole or part of the ligand binding region. The ligand binding region of PDGFR-alpha is a 125 amino acid sequence of the extracellular or transmembrane region of PDGFR-alpha. The inventors have identified the region of interaction between the ligand (PDGFA) and the PDGFR-alpha receptor. They have designed short peptide fragments to cover the 125 amino acid ligand sequence which may optionally comprise an additional moiety such as an ASO. In one embodiment, the peptide ligand may bind within the canonical binding site of PDGFR- alpha for PDGFA (SEQ ID NO: 31). In another embodiment, the peptide ligand may bind outside the canonical binding site of PDGFR-alpha for PDGFA (SEQ ID NO: 31). In one embodiment the extracellular or transmembrane region of PDGFR-alpha may be expressed by fibroblasts. In one embodiment the fibroblast may be from the list of gingival fibroblast, bladder fibroblast, lung fibroblast, uterine fibroblast, dermal fibroblast, muscle fibroblast (MIF), cardiac fibroblast, fibroblast within colon. In one embodiment the fibroblasts may be MIFs. In one embodiment the peptides bind fibroblasts and/or podocytes, and/or cells originating from tissues selected from the list of liver, kidney, skeletal muscle, neural and/or endothelium. In one embodiment, the cells originating from liver tissues comprise liver cells. In one embodiment, the cells originating from kidney tissues comprise podocytes. In one embodiment, the cells originating from endothelial tissues comprise endothelial cells, umbilical vein endothelial cells and/or glomerular endothelial cells. In one embodiment, the cells originating from neural tissues comprise neural cells. In one embodiment, the peptide ligand comprises SEQ ID NO: 2 or a peptide ligand sequence having at least 80% homology thereto and binds, or preferably binds, or specifically binds fibroblasts and/or cells originating from kidney tissue. In one embodiment, the peptide ligand comprises SEQ ID NO: 3 or a peptide ligand sequence having at least 80% homology thereto and binds, or preferably binds, or specifically binds fibroblasts. In one embodiment, the peptide ligand comprises SEQ ID NO: 4 or a peptide ligand sequence having at least 80% homology thereto and binds, or preferably binds, or specifically binds fibroblasts. In one embodiment, the peptide ligand comprises SEQ ID NO: 5 or a peptide ligand sequence having at least 80% homology thereto and binds, or preferably binds, or specifically binds cells originating from skeletal muscle tissue, cells originating from kidney tissue and/or cells originating from endothelial tissue. In one embodiment, the peptide ligand comprises SEQ ID NO: 6 or a peptide ligand sequence having at least 80% homology thereto and binds, or preferably binds, or specifically binds fibroblasts and/or cells originating from skeletal muscle tissue. In one embodiment, the peptide ligand comprises SEQ ID NO: 7 or a peptide ligand sequence having at least 80% homology thereto and binds, or preferably binds, or specifically binds fibroblasts, cells originating from skeletal muscle tissue, cells originating from endothelial tissue and/or cells originating from kidney tissue. In one embodiment, the peptide ligand comprises SEQ ID NO: 8 or a peptide ligand sequence having at least 80% homology thereto and binds, or preferably binds, or specifically binds cells originating from endothelial tissue and/or cells originating from kidney tissue. In one embodiment, the peptide ligand comprises SEQ ID NO: 9 or a peptide ligand sequence having at least 80% homology thereto and binds, or preferably binds, or specifically binds cells originating from skeletal muscle tissue and/or cells originating from kidney tissue. In one embodiment, the peptide ligand comprises SEQ ID NO: 10 or a peptide ligand sequence having at least 80% homology thereto and binds, or preferably binds, or specifically binds cells originating from endothelial tissue and/or cells originating from kidney tissue. In one embodiment, the peptide ligand comprises SEQ ID NO: 11 or a peptide ligand sequence having at least 80% homology thereto and binds, or preferably binds, or specifically binds cells originating from kidney tissue. In one embodiment, the peptide ligand comprises SEQ ID NO: 12 or a peptide ligand sequence having at least 80% homology thereto and binds, or preferably binds, or specifically binds cells originating from endothelial tissue, cells originating from liver tissue and/or fibroblasts. In one embodiment, the peptide ligand comprises SEQ ID NO: 13 or a peptide ligand sequence having at least 80% homology thereto and binds, or preferably binds, or specifically binds cells originating from endothelial tissue, cells originating from liver tissue, cells originating from skeletal muscle tissue, kidney cells, cells originating from neural tissue and/or fibroblasts. A peptide ligand of the invention described herein, which “binds” or is “capable of binding” an antigen of interest, e.g. the extracellular or transmembrane region of human PDGFR-alpha, or the cell of interest, e.g. the fibroblast, is one that binds the antigen or cell with sufficient affinity such that the peptide ligand is useful as a therapeutic agent in targeting a cell or tissue expressing the antigen human PDGFR-alpha as described herein. Peptide ligands of the invention of the invention, which “preferentially binds” or is “capable of preferentially binding” an antigen of interest, e.g. the extracellular or transmembrane region of human PDGFR-alpha, or the cell of interest, e.g. the fibroblast, is one that binds the antigen or cell to a greater degree than other antigens or cells. In other words, the binding is measurably different from the binding to other antigens or cells. Peptide ligands of the invention of the invention, which “specifically binds” or "specifically binds to" or is "specific for" an antigen of interest, e.g. the extracellular or transmembrane region of human PDGFR-alpha, or the cell of interest, e.g. the fibroblast, as used herein can be exhibited, for example, by a peptide having a KD for the target of at least about 10-6 M, alternatively at least about 10-7 M, alternatively at least about 10-8 M, alternatively at least about 10-9 M, alternatively at least about 10-10 M, alternatively at least about 10-11 M, alternatively at least about 10-12 M, or lower. In one embodiment, the term “specifically binds” refers to binding where a peptide binds to a particular polypeptide or epitope on a particular polypeptide without substantially binding to any other polypeptide or polypeptide epitope. In one embodiment, the peptide ligand may be internalised upon binding to the extracellular or transmembrane region of PDGFR-alpha. As used herein, “internalized” means any cellular process where substances (e.g. the peptide ligand) are brought into the cell, such as via endocytosis, phagocytosis and pinocytosis. In one embodiment, the peptide ligand may be conjugated to another moiety. As used herein, the moiety may be selected from a toxin, enzyme, radioisotope, half-life extending moiety, label, therapeutic molecule or other chemical moiety. It should be appreciated that various types of moiety may be conjugated to the peptide ligand. For example, the moiety may comprise, or consist of, -lactamase, (i-galactosidase (LacZ), alkaline phosphatase, thymidine kinase, green fluorescent protein (GFP), chloramphenicol acetyltransferase (CAT), luciferase, membrane bound proteins including, for example, CD2, CD4, CD8, the influenza hemagglutinin protein, and others well known in the art, to which high affinity antibodies directed thereto exist or can be produced by conventional means, and fusion proteins comprising a membrane bound protein appropriately fused to an antigen tag domain from, among others, hemagglutinin or Myc. These moieties provide signals detectable by conventional means, including enzymatic, radiographic, colorimetric, fluorescence or other spectrographic assays, fluorescent activating cell sorting assays and immunological assays, including enzyme linked immunosorbent assay (ELISA), radioimmunoassay (RIA) and immunohistochemistry. In another example, the therapeutic molecule may comprise, or consist of, a nucleic acid (e.g., DNA or RNA), a peptide (e.g., an antibody), a lipid (e.g., a micro vesicle), small molecule, or a sugar moiety (e.g., a polysaccharide). Preferably, the therapeutic molecule may be an RNA or DNA oligonucleotide. Preferably still, the RNA or DNA oligonucleotide may be an antisense oligonucleotide (ASO), a small interfering RNA (siRNA) or a small activating RNA (saRNA). Wherein the term small activating RNA is used, short activating RNA is also used. The terms are used interchangeably. Where the therapeutic molecule is an ASO, siRNA or saRNA, the ASO, siRNA or saRNA is capable of hybridizing to a target nucleic acid, resulting in at least one antisense or siRNA activity. In certain embodiments, the antisense or siRNA activity may reduce or inhibit the amount or activity of a target nucleic acid. In certain embodiments, the antisense or saRNA may increase the expression of a target nucleic acid. In certain embodiments, antisense, siRNA or saRNA compounds selectively affect one or more target nucleic acid. Such antisense, siRNA or saRNA compounds comprise a nucleotide sequence that hybridizes to one or more target nucleic acid, resulting in one or more desired antisense, siRNA or saRNA activity and does not hybridize to one or more non-target nucleic acid or does not hybridize to one or more non-target nucleic acid in such a way that results in significant undesired antisense, siRNA or saRNA activity. The therapeutic molecule may be any therapeutic molecule known in the art. The therapeutic molecule is not considered to be a limitation of the invention. For example, if the therapeutic molecule is an ASO, any generation or type of ASO may be used. For example, the phosphorodiamidate morpholino oligomers (PMOs) and the phosphorothioates (PSs) backbones may be used. In one embodiment, the ASO comprises SEQ ID NO: 35 or SEQ ID NO: 36. In certain antisense activities, hybridization of an antisense compound to a target nucleic acid results in recruitment of a protein that cleaves the target nucleic acid. For example, certain antisense compounds result in RNase H mediated cleavage of the target nucleic acid. RNase H is a cellular endonuclease that cleaves the RNA strand of an RNA:DNA duplex. The DNA in such an RNA:DNA duplex need not be unmodified DNA. In certain embodiments, antisense compounds described herein are sufficiently “DNA-like” to elicit RNase H activity. In certain embodiments, one or more non-DNA-like nucleoside the gap of a gapmer is tolerated. In certain siRNA activities, an siRNA compound or a portion of an siRNA compound is loaded into an RNA-induced silencing complex (RISC), ultimately resulting in cleavage of the target nucleic acid. For example, certain siRNA compounds result in cleavage of the target nucleic acid by Argonaute. In certain embodiments, hybridization of an antisense or siRNA compound to a target nucleic acid does not result in recruitment of a protein that cleaves that target nucleic acid. In certain embodiments, hybridization of the antisense or siRNA compound to the target nucleic acid results in alteration of splicing of the target nucleic acid. In certain embodiments, hybridization of an antisense or siRNA compound to a target nucleic acid results in inhibition of a binding interaction between the target nucleic acid and a protein or other nucleic acid. In certain embodiments, hybridization of an antisense or siRNA compound to a target nucleic acid results in alteration of translation of the target nucleic acid. In certain embodiments, the target nucleic acid is an endogenous RNA molecule. In certain embodiments, the target nucleic acid is an endogenous DNA molecule. In certain embodiments, the target nucleic acid encodes a protein. In certain such embodiments, the target nucleic acid is selected from: a mature mRNA and a pre-mRNA, including intronic, exonic and untranslated regions. In certain embodiments, the target RNA is a mature mRNA. In certain embodiments, the target nucleic acid is a pre-mRNA. In certain such embodiments, the target region is entirely within an intron. In certain embodiments, the target region spans an intron/exon junction. In certain embodiments, the target region is at least 50% within an intron. In certain embodiments, the target nucleic acid is the RNA transcriptional product of a retrogene. In certain embodiments, the target nucleic acid is a non-coding RNA. In certain such embodiments, the target non-coding RNA is selected from: a long noncoding RNA, a short non-coding RNA, an intronic RNA molecule. In another embodiment, the peptide ligand is directly conjugated to the moiety. In another embodiment, the peptide ligand is indirectly conjugated to the moiety. As used herein, “indirectly conjugated” means the peptide ligand is conjugated to the moiety via a bridge such as a peptide extender or linker. In another embodiment, the bridge is cleavable. In another embodiment, the bridge is not cleavable (e.g. may comprise an alkane linker such as sulfosuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate) linker, maleimide linker or n-hydroxysuccinimide ester). In one embodiment, the linker may be a SMCC crosslinker (Succinimidyl-4- [N-maleimidomethyl]cyclohexane-1-carboxylate). In some embodiments, the cleavable bridge may comprise a protease- sensitive linker, pH-sensitive linker, or glutathione- sensitive linker. A protease-sensitive linker may comprise a sequence cleavable by a lysosomal protease and/or an endosomal protease. In some embodiments, a protease- sensitive linker comprises a valine-citrulline dipeptide sequence. A pH-sensitive linker may be cleaved at a pH in a range of 4 to 6. Methods of conjugated or chemically coupling molecules are known by those skilled in the art. The use of PDGFR-alpha targeting peptide ligands may be useful for concentrating a molecular payload (e.g. an ASO or siRNA) in fibroblasts (for example in muscle) while reducing toxicity associated with effects in other tissues. In some embodiments, the PDGFR-alpha peptide ligands concentrate a bound molecular payload in MIF located in the muscle tissue as compared to another tissue type within a subject. In some embodiments, the PDGFR-alpha peptide ligands concentrates a bound molecular payload in fibroblasts (e.g., MIFs) in an amount that is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, or 100 times greater than an amount in non-fibroblasts (e.g., liver, neuronal, blood, or fat cells). In some embodiments, a toxicity of the molecular payload in a subject is reduced by at least 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 90%, or 95% when it is delivered to the subject when bound to the PDGFR-alpha peptide ligands. In some embodiments the peptide ligands may be useful for concentrating a molecular payload (e.g. an ASO or siRNA) in podocytes, and/or cells originating from tissues selected from list of liver, kidney and/or endothelium while reducing toxicity associated with effects in other tissues. In some embodiments, the peptide ligands concentrate a bound molecular payload in podocytes, and/or cells originating from tissues selected from list of liver, kidney and/or endothelium as compared to another tissue type within a subject. In some embodiments, the peptide ligands concentrate a bound molecular payload in an amount that is at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, or 100 times greater than an amount in said other tissue type. In some embodiments, a toxicity of the molecular payload in a subject is reduced by at least 1%, 2%, 3%, 4%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 90%, or 95% when it is delivered to the subject when bound to the peptide ligands. In another aspect, the invention comprises a pharmaceutical composition comprising a peptide ligand according to the invention and optionally a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier or vehicle can be particulate, so that the compositions are, for example, in tablet or powder form. The term "carrier" refers to a diluent, adjuvant or excipient, with which a peptide ligand of the present invention is administered. Such pharmaceutical carriers can be liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like. The carriers can be saline, gum acacia, gelatin, starch paste, talc, keratin, colloidal silica, urea, and the like. In addition, auxiliary, stabilizing, thickening, lubricating and coloring agents can be used. In one embodiment, when administered to an animal, the antibody or fragment thereof of the present invention or compositions and pharmaceutically acceptable carriers are sterile. Water is a preferred carrier when the peptide ligands of the present invention are administered intravenously. Saline solutions and aqueous dextrose and glycerol solutions can also be employed as liquid carriers, particularly for injectable solutions. Suitable pharmaceutical carriers also include excipients such as starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. The present compositions, if desired, can also contain minor amounts of wetting or emulsifying agents, or pH buffering agents. The pharmaceutical composition of the invention can be in the form of a liquid, e.g., a solution, emulsion or suspension. The liquid can be useful for delivery by injection, infusion (e.g., IV infusion) or subcutaneously. When intended for oral administration, the composition is preferably in solid or liquid form, where semi-solid, semi-liquid, suspension and gel forms are included within the forms considered herein as either solid or liquid. As a solid composition for oral administration, the composition can be formulated into a powder, granule, compressed tablet, pill, capsule, chewing gum, wafer or the like form. Such a solid composition typically contains one or more inert diluents. In addition, one or more of the following can be present: binders such as carboxymethylcellulose, ethyl cellulose, microcrystalline cellulose, or gelatin; excipients such as starch, lactose or dextrins, disintegrating agents such as alginic acid, sodium alginate, corn starch and the like; lubricants such as magnesium stearate; glidants such as colloidal silicon dioxide; sweetening agents such as sucrose or saccharin; a flavoring agent such as peppermint, methyl salicylate or orange flavoring; and a coloring agent. When the composition is in the form of a capsule (e. g. a gelatin capsule), it can contain, in addition to materials of the above type, a liquid carrier such as polyethylene glycol, cyclodextrin or a fatty oil. The composition can be in the form of a liquid, e. g. an elixir, syrup, solution, emulsion or suspension. The liquid can be useful for oral administration or for delivery by injection. When intended for oral administration, a composition can comprise one or more of a sweetening agent, preservatives, dye/colorant and flavor enhancer. In a composition for administration by injection, one or more of a surfactant, preservative, wetting agent, dispersing agent, suspending agent, buffer, stabilizer and isotonic agent can also be included. Compositions can take the form of one or more dosage units. In specific embodiments, it can be desirable to administer the composition locally to the area in need of treatment, or by injection, intravenous injection or infusion, or subcutaneous injection, or by lumbar puncture in the cerebro-spinal fluid (CSF) In another aspect, the invention comprises a method for treating a cancer, an immune disorder, a respiratory disorder, metabolic disorder, inflammatory disorder, allergy, transplant rejection, viral infection, muscular dystrophy and/or neuromuscular disease, immune deficiency, and other immune system-related disorder comprising administering a therapeutically effective amount of a peptide ligand according to the invention or a pharmaceutical composition according to the invention. In one embodiment the muscular dystrophy and/or neuromuscular disease may be selected from a congenital muscular dystrophy or myopathy, Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, tibial muscular dystrophy, distal muscular dystrophy, and Emery-Dreifuss muscular dystrophy. In another embodiment the muscular dystrophy and/or neuromuscular disease may be a congenital muscular dystrophy or myopathy resulting from mutations in any of the three collagen VI genes (COL6A1, COL6A2, COL6A3), clinically known as Ullrich congenital muscular dystrophy or Bethlem myopathy and intermediate clinical manifestations. In another embodiment fibrosis may be targeted in the muscular dystrophy selected from a congenital muscular dystrophy or myopathy, Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, tibial muscular dystrophy, distal muscular dystrophy, and Emery-Dreifuss muscular dystrophy. In another embodiment the cancer may be selected from bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, kidney cancer, sarcoma of soft tissue, cancer of the urethra, cancer of the bladder, renal cancer, lung cancer, non-small cell lung cancer, thymoma, urothelial carcinoma leukemia, prostate cancer, mesothelioma, adrenocortical carcinoma, lymphomas, such as such as Hodgkin's disease, non-Hodgkin's, gastric cancer, and multiple myelomas. As used herein, “administering” means providing a pharmaceutical agent to an animal. As used herein, “animal” means a human or non-human animal. In certain embodiments, the animal is a human. The amount of the therapeutic that is effective/active in the treatment of a particular disorder or condition will depend on the nature of the disorder or condition and the animal to be treated and can be determined by standard clinical techniques. In addition, in vitro or in vivo assays can optionally be employed to help identify optimal dosage ranges. The precise dose to be employed in the compositions will also depend on the route of administration, and the seriousness of the disease or disorder, and should be decided according to the judgment of the practitioner and each subject's circumstances. Factors like age, body weight, sex, diet, time of administration, rate of excretion, condition of the host, drug combinations, reaction sensitivities and severity of the disease shall be taken into account. Preferably the peptide ligand is administered in a therapeutically effective amount. A "therapeutically-effective" amount as used herein is an amount of that is sufficient to alleviate (e.g., mitigate, decrease, reduce) at least one of the symptoms associated with a disease state. Alternatively stated, a "therapeutically-effective" amount is an amount that is sufficient to provide some improvement in the condition of the subject. A "therapeutically effective amount" will fall in a relatively broad range that can be determined through experimentation and/or clinical trials. In another aspect, the invention comprises a use of a peptide ligand according to the invention or a pharmaceutical composition according to the invention in the manufacture of a medicament for the treatment of a cancer, an immune disorder, a respiratory disorder, metabolic disorder, inflammatory disorder, allergy, transplant rejection, viral infection, muscular dystrophy, immune deficiency, and other immune system-related disorder comprising administering a therapeutically effective amount of a peptide ligand according to the invention or a pharmaceutical composition according to the invention. In one embodiment the muscular dystrophy may be selected from a congenital muscular dystrophy or myopathy, Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, tibial muscular dystrophy, distal muscular dystrophy, and Emery-Dreifuss muscular dystrophy. In another embodiment the muscular dystrophy may be a congenital muscular dystrophy or myopathy resulting from mutations in any of the three collagen VI genes (COL6A1, COL6A2, COL6A3), clinically known as Ullrich congenital muscular dystrophy or Bethlem myopathy and intermediate clinical manifestations. In another embodiment fibrosis may be targeted in the muscular dystrophy selected from a congenital muscular dystrophy or myopathy, Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, tibial muscular dystrophy, distal muscular dystrophy, and Emery-Dreifuss muscular dystrophy. In another embodiment the cancer may be selected from bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, kidney cancer, sarcoma of soft tissue, cancer of the urethra, cancer of the bladder, renal cancer, lung cancer, non-small cell lung cancer, thymoma, urothelial carcinoma leukemia, prostate cancer, mesothelioma, adrenocortical carcinoma, lymphomas, such as such as Hodgkin's disease, non-Hodgkin's, gastric cancer, and multiple myelomas. In another aspect, the invention comprises a peptide ligand according to the invention or a pharmaceutical composition according to the invention for use as a treatment. In another aspect, the invention comprises a peptide ligand according to the invention or a pharmaceutical composition according to the invention for use as a treatment for cancer, an immune disorder, a respiratory disorder, metabolic disorder, inflammatory disorder, allergy, transplant rejection, viral infection, muscular dystrophy and/or neuromuscular disease, immune deficiency, and other immune system-related disorder comprising administering a therapeutically effective amount of a peptide ligand according to the invention or a pharmaceutical composition according to the invention. In one embodiment the muscular dystrophy and/or neuromuscular disease may be selected from a congenital muscular dystrophy or myopathy, Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, tibial muscular dystrophy, distal muscular dystrophy, and Emery-Dreifuss muscular dystrophy. In another embodiment the muscular dystrophy and/or neuromuscular disease may be a congenital muscular dystrophy or myopathy resulting from mutations in any of the three collagen VI genes (COL6A1, COL6A2, COL6A3), clinically known as Ullrich congenital muscular dystrophy or Bethlem myopathy and intermediate clinical manifestations. In another embodiment fibrosis may be targeted in the muscular dystrophy and/or neuromuscular disease selected from a congenital muscular dystrophy or myopathy, Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, tibial muscular dystrophy, distal muscular dystrophy, and Emery-Dreifuss muscular dystrophy. In another embodiment the cancer may be selected from bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, breast cancer, brain cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, kidney cancer, sarcoma of soft tissue, cancer of the urethra, cancer of the bladder, renal cancer, lung cancer, non-small cell lung cancer, thymoma, urothelial carcinoma leukemia, prostate cancer, mesothelioma, adrenocortical carcinoma, lymphomas, such as such as Hodgkin's disease, non-Hodgkin's, gastric cancer, and multiple myelomas. The peptide ligand or pharmaceutical composition may be administered as the sole active ingredient or in combination with one or more other drug, e.g., an immunosuppressive or immunomodulating agent or other anti-inflammatory agent, e.g., for the treatment or prevention of diseases mentioned above. The peptide ligand or pharmaceutical composition of the invention may be administered at the same time or at a different time as the other drug e.g., simultaneously, separately or sequentially. In another aspect, the invention comprises or consists of a nucleic acid molecule comprising or consisting of a nucleotide sequence encoding a peptide ligand according to the invention. In one embodiment the nucleic acid molecule may comprise or consist of a nucleotide sequence encoding a peptide ligand according to the invention selected from SEQ ID NO: 15 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 16 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 17 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 18 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 19 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 20 or a nucleotide having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 21 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 22 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 23 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 24 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 25 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 26 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 27 or a nucleotide sequence having at least 80% homology thereto. In another embodiment the sequence homology is at least 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99%. In one embodiment, the N-terminus and/or C- terminus additionally comprises nucleotides encoding at least one positively charged residue. In another aspect, the invention comprises a vector comprising a nucleic acid according to the invention. A “vector” is any nucleic acid molecule for the cloning of and/or transfer of a nucleic acid into a cell. A vector may be a replicon to which another nucleotide sequence may be attached to allow for replication of the attached nucleotide sequence. A “replicon” can be any genetic element (e.g., plasmid, phage, cosmid, chromosome, viral genome) that functions as an autonomous unit of nucleic acid replication in vivo, i.e., capable of replication under its own control. The term “vector” includes both viral and nonviral (e.g., plasmid) nucleic acid molecules for introducing a nucleic acid into a cell in vitro, ex vivo, and/or in vivo. In another aspect, the invention comprises a host cell comprising a nucleic acid according to the invention or a vector according to the invention. In one embodiment the host cell may be a bacterial, yeast, insect, plant, viral or mammalian cell. In another aspect the invention comprises a method for producing the peptide ligand of the invention comprising a nucleic acid encoding said peptide ligand in a host cell and isolating the peptide ligand from the host cell. In another aspect the invention comprises a system to identify peptide ligand sequences which can specifically bind to PDGFR-alpha for drug delivery, comprising the steps of identifying a cell-surface epitope, design of peptide ligand sequence capable of binding at the PDGF-alpha- PDGFR-alpha interface, and uptake and/or internalisation of the peptide ligand by the host cell. In the above method, the identification of a suitable a cell-surface epitope may be readily selected by one of skill in the art. The selection of the method of identification is not considered to be a limitation of this invention. For example, the method of identification may be at the RNA level e.g. using an RNA sequencing (RNA-seq) database such as a single cell RNA-seq (scRNA-seq) database, or the method of identification may be at the protein level e.g. using mass spectrometry. In the above method, the design of peptide ligand sequence capable of binding at the PDGF- alpha-PDGFR-alpha interface may be achieved by any one of a number of techniques which may be readily selected by one of skill in the art. The selection of the technique of characterisation is not considered to be a limitation of this invention. For example, suitable methods may include but are not limited to analysing the 3D structure of the cell-surface protein so as to identify the primary ligand binding region. In another aspect the invention comprises a multimeric binding complex comprising at least two of the peptide ligands according to the invention. In one embodiment the at least two peptide ligands may be connected by at least one bridge. Peptide ligands in a multimeric binding complex can be the same (e.g. identical) or different (e.g., comprise at least 1 amino acid difference). In some embodiments the at least one amino acid difference may comprise at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 21, at least 22 amino acids. In some embodiments, multimers comprise 2 or more peptide ligands linked together by a cleavable linker. However, in some embodiments, multimers comprise 2 or more peptide ligands linked together by a non-cleavable linker. In some embodiments, a multimer comprises 2, 3, 4, 5, 6, 7, 8, 9, 10 or more peptide ligands linked together. In some embodiments, a multimer comprises 2 to 5, 2 to 10 or 4 to 20 peptide ligands linked together. In one embodiment the multimeric binding complex may comprise an additional moiety. In another embodiment the additional moiety may be selected from a toxin, enzyme, radioisotope, half-life extending moiety, label, therapeutic molecule or other chemical moiety. In another embodiment the therapeutic molecule may be an RNA or DNA oligonucleotide. In another embodiment the RNA or DNA oligonucleotide is may be an ASO, siRNA or saRNA. In another aspect the invention comprises a tissue delivery complex which comprises a peptide ligand according to the invention or a multimeric binding complex according to the invention. In one embodiment the tissue delivery complex may be a muscle tissue delivery complex. In another embodiment the tissue delivery complex may be a liver, kidney and/or endothelium delivery complex. In another embodiment the tissue delivery complex according to the invention may be for the use in the treatment of muscular dystrophy and/or neuromuscular disease, and/or diseases of the liver, kidney and/or endothelium. In another embodiment the muscular dystrophy and/or neuromuscular disease may be a congenital muscular dystrophy or myopathy, Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, tibial muscular dystrophy, distal muscular dystrophy, and Emery-Dreifuss muscular dystrophy. In another embodiment fibrosis may be targeted in the muscular dystrophy and/or neuromuscular disease selected from a congenital muscular dystrophy or myopathy, Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, tibial muscular dystrophy, distal muscular dystrophy, and Emery-Dreifuss muscular dystrophy. In another embodiment the muscular dystrophy and/or neuromuscular disease may be a congenital muscular dystrophy or myopathy resulting from mutations in any of the three collagen VI genes (COL6A1, COL6A2, COL6A3), clinically known as Ullrich congenital muscular dystrophy or Bethlem myopathy and intermediate clinical manifestations. In another aspect the invention comprises a method of modifying the expression of a target gene in a fibroblast comprising providing to the cell an ASO, siRNA or saRNA conjugated to a peptide ligand according to the invention. Suitable target genes may be readily selected by one of skill in the art. For example, for collagen VI- related dystrophies the target genes may be COL6A1, COL6A2 and/or COL6A3. The selection of the target gene is not considered to be a limitation of this invention. In another aspect the invention comprises a kit comprising the peptide ligand according to the invention or a pharmaceutical composition according to the invention and optionally instructions for use. The kit may be useful for the treatment and/or prevention of a disease described above. In another aspect the invention comprises a therapeutic molecule comprising the peptide ligand according to the invention. In another embodiment, the additional moiety may be selected from a toxin, enzyme, radioisotope, half-life extending moiety, label, therapeutic molecule or other chemical moiety. In one embodiment the therapeutic molecule may be an RNA or DNA oligonucleotide. In one embodiment the RNA or DNA oligonucleotide may be an antisense oligonucleotide or a small interfering RNA. In another aspect the invention comprises a method of delivering to a fibroblast and/or podocyte and/or cells originating from tissues selected from list of liver, kidney, skeletal muscle and/or endothelium apeptide ligand according to the invention, the pharmaceutical composition according to the invention, or the therapeutic molecule according to the invention. The method of delivery may be an in vitro method, an ex vivo method or an in vivo method. The method of delivery may be readily selected by one of skill in the art. The selection of the method of delivery is not considered to be a limitation of this invention. In another aspect the invention comprises a method of screening for the peptide ligand according to the invention. Methods for preparing or generating the peptide ligands, nucleic acids, host cells, products and compositions described herein using in vitro expression libraries can comprise the steps of: a) providing a set, collection or library of nucleic acid sequences encoding amino acid sequences; and b) screening said set, collection or library for amino acid sequences that can bind the extracellular or transmembrane region of PDGFR-alpha according to the invention; and c) isolating the amino acid sequence(s) that can bind the extracellular or transmembrane region of PDGFR-alpha according to the invention. In the above method, the set, collection or library of amino acid sequences may be displayed on a phage, phagemid, ribosome or suitable micro-organism (such as yeast), such as to facilitate screening. Suitable methods, techniques and host organisms for displaying and screening (a set, collection or library of) amino acid sequences will be clear to the person skilled in the art (see for example Phage Display of Peptides and Proteins: A Laboratory Manual, Academic Press; 1st edition (October 28, 1996) Brian K. Kay, Jill Winter, John McCafferty). Libraries, for example phage libraries, are generated by isolating a cell or tissue expressing an antigen-specific ligand, cloning the sequence encoding the antigen-specific ligand from mRNA derived from the isolated cell or tissue and displaying the encoded protein using a library. The antigen-specific ligand(s) can be expressed in bacterial, yeast or other expression systems. Alternatively, suitable methods of screening the peptides may include functional assays as shown in the examples. For example, a suitable functional assay can comprise the steps of: a) identifying suitable cell-surface proteins expressed in fibroblasts for use in screening assays; and b) characterising the suitable cell-surface proteins; and c) screening fibroblasts with a set, collection or library of peptides In the above method, the identification of suitable cell surface proteins may be readily selected by one of skill in the art. The selection of the method of identification is not considered to be a limitation of this invention. For example, the method of identification may be at the RNA level e.g. using an RNA sequencing (RNA-seq) database such as a single cell RNA-seq (scRNA- seq) database, or the method of identification may be at the protein level e.g. using mass spectrometry. For example, the method may comprise analysing a first single-cell RNA sequencing dataset of a first cell population to identify genes encoding cell surface proteins from the first cell population and/or analysing a surfaceome dataset of said first cell population to identify cell-surface proteins from the first cell population, comparing the first single-cell RNA sequencing and/or surfaceome dataset(s) to a second dataset, and excluding the cell surface proteins highly expressed in liver and/or kidneys. The dataset may be derived from a public database such as the Human Cell Landscape database (http://bis.zju.edu.cn/HCL/) or experimentally derived. In one embodiment the method may comprise the identification of a target that is specifically or more abundantly expressed in the first cell population. To screen for a muscle targeting peptide therefore, the method may comprise analysing a single-cell RNA sequencing dataset deposited in the Human Cell Landscape database from an adult muscle and a foetal single-cell RNA sequencing dataset to identify genes encoding cell surface proteins from MIFs. The method may also comprise analysing a dataset from liver and kidney populations and excluding the cell-surface proteins highly expressed in these tissues to de- target them. Similarly, the data may then be compared with experimentally derived surfaceome data which may generated by purifying cell-surface proteins from muscle cells (such as MIFs, myoblasts and fibroblasts) and HepG2 cell lines, followed by mass spectrometry analysis. This analysis can be used to identify exclusively expressed in MIFs and not in myoblasts or HepG2. In the above methods, the characterisation of the suitable cell-surface proteins may be achieved by any one of a number of techniques which may be readily selected by one of skill in the art. The selection of the technique of characterisation is not considered to be a limitation of this invention. For example, the method of characterisation may be at the RNA level e.g. using real time polymerase chain reaction to detect transcripts of the cell-surface proteins in candidate cells. Alternatively, the method of characterisation may be at the protein level, such as using immunofluorescence microscopy where candidate cells such as fibroblasts are stained with an antibody towards the cell-surface protein. In the above method, the method of screening of fibroblasts with a set, collection or library of peptides may be readily selected by one of skill in the art. The selection of the method of identification is not considered to be a limitation of this invention. For example, the set, collection or library of peptides suitable for binding said cell-surface proteins may be conjugated with a label or marker which allows for their detection by conventional means, including enzymatic, radiographic, colorimetric, fluorescence or other spectrographic assays, fluorescent activating cell sorting assays and immunological assays, including enzyme linked immunosorbent assay (ELISA), radioimmunoassay (RIA) and immunohistochemistry. Suitable peptides may be identified by suitable methods readily available to one of skill in the art. Suitable methods may include but are not limited to analysing the 3D structure of the cell- surface protein so as to identify the primary ligand binding region. In another aspect the invention comprises a method for targeting fibroblasts comprising administering a peptide ligand according to the invention or a pharmaceutical composition according to the invention, wherein the peptide ligand targets an extracellular or transmembrane region of PDGFR-alpha. The method of administration may be an in vitro method, an ex vivo method or an in vivo method. The method of administration may be readily selected by one of skill in the art. The selection of the method of administration is not considered to be a limitation of this invention. Unless otherwise defined herein, scientific and technical terms used in connection with the present disclosure shall have the meanings that are commonly understood by those of ordinary skill in the art. While the foregoing disclosure provides a general description of the subject matter encompassed within the scope of the present invention, including methods, as well as the best mode thereof, of making and using this invention, the following examples are provided to further enable those skilled in the art to practice this invention and to provide a complete written description thereof. However, those skilled in the art will appreciate that the specifics of these examples should not be read as limiting on the invention, the scope of which should be apprehended from the claims and equivalents thereof appended to this disclosure. Various further aspects and embodiments of the present invention will be apparent to those skilled in the art in view of the present disclosure. All documents mentioned in this specification are incorporated herein by reference in their entirety, including references to gene accession numbers. "and/or" where used herein is to be taken as specific disclosure of each of the two specified features or components with or without the other. For example, "A and/or B" is to be taken as specific disclosure of each of (i) A, (ii) B and (iii) A and B, just as if each is set out individually herein. Unless context dictates otherwise, the descriptions and definitions of the features set out above are not limited to any particular aspect or embodiment of the invention and apply equally to all aspects and embodiments which are described. Examples The invention is further described in the non-limiting examples. Example 1 The skeletal muscle cellulome was decoded using single-cell RNA sequencing (scRNA-Seq) public dataset deposited in Human Cell Landscape. Among these genes, a potential MIF cell- surface target, encoding a surface receptor which belongs to the α subunit of the platelet- derived growth factor receptors (PDGFRα) family, was identified (Figure 1). Immunofluorescence staining of PDGFRα performed by the inventors confirmed a strong expression in fibroblasts isolated from skin and skeletal muscle, but not in myoblasts or liver cells. These data were also confirmed at the mRNA level (Figure 2). The 3D structures of PDGFRα and its ligand (PDGF-A) were analysed, which allow us to identify the region of interaction between the ligand and the receptor. The academic team have identified a 125 amino acid sequence which can bind to the primary ligand binding region. They have designed 13 short peptide fragments, 22-aa each with overlapped sequence to each other, to cover the 125 amino acid ligand sequence, and 1 peptide (peptide 13) consisting of 15 amino acids (table 1). These 13 short peptides were tagged with the FAM fluorophore at the N terminal. The uptake and internalization of the 13 fluorescent peptides were evaluated in a list of human and mouse cell lines, including human skin fibroblasts, endothelial cells (HUVEC) and hepatocytes (HepG2 line), mouse skin fibroblasts (NIH 3T3 line) and myoblasts (C2C12 line), human and mouse podocytes (kidney). Furthermore, the abilities of binding and internalization of these peptides in different type of cells have been profiled (Figure 3). For MIF targeting, the peptide sequences that showed strong binding and internalization in fibroblasts from both human and mouse, but not in other cell types such as human hepatocytes, podocytes and myoblasts, have been identified (Figure 3 and 4). Screening methodology The inventors analyzed the public dataset of single-cell RNA sequencing (scRNA-Seq) deposited in the Human Cell Landscape database (http://bis.zju.edu.cn/HCL/). Specifically, scRNA-seq data from an adult muscle and a foetal muscle were analyzed through the HCL website. From this analysis, the inventors identified the population of MIFs and the genes expressed in them, among the other cell populations present in skeletal muscle. Next, the inventors analyzed the cellular localization of proteins encoded by the 600 genes expressed in MIFs using Ingenuity Pathway Analysis (IPA), which identified 64 genes encoding plasma membrane proteins. The inventors then excluded the cell-surface proteins highly expressed in liver and kidneys to de-target these tissues. This led to the identification of 20 genes encoding for cell-surface proteins expressed specifically or more abundantly in MIFs. The data obtained at the RNA level were then compared with a second set of data, the surfaceome data. The surfaceome data was generated by purifying cell-surface proteins from MIFs, myoblasts, fibroblasts (both controls and COL6 patients), and HepG2 (human hepatocyte line) cell lines, respectively, followed by mass spectrometry analysis. The inventors identified 19 proteins that were exclusively expressed in MIFs and not in myoblasts or HepG2. Among these, the inventors identified 6 proteins that were also present in skin fibroblasts from both healthy control and COL6 patients. Among these 6 proteins, the inventors have selected PDGFRα as a potential target for fibroblast-specific drug delivery while reducing the potential exposure of liver and kidney to the delivery. Example 2 The specificity of 13 peptides designed based on the PDGFA ligand sequence has been tested in an additional 6 cell lines (4 human and 2 mouse cell lines), bringing the total to 14 different cell lines, as listed in the table below. These additional data validated our earlier findings, with two peptide sequences (peptide-3 and peptide-5) demonstrating a preferential ability to target fibroblasts (Figure 5). Peptide-3 and peptide-5 were further examined in human and mouse fibroblasts at various time points, showing their efficiency in targeting fibroblasts within just 10 minutes post-incubation (Figure 6). Table 1: 9 human and 5 mouse cell lines were used to test 13 different peptides. In red are shown primary cell lines. To confirm the internalization of peptide-3 and peptide-5 into fibroblasts, we employed two imaging techniques. Z-stack images captured using a confocal microscope showed that the peptide signal originates from the cytoplasm rather than from the cell surface of the fibroblasts (Figure 7A (i)). The same results have been shown with the time-lapse videos, where it was observed that after a 15-minute incubation, the peptides were able to bind to the cell surface of the fibroblasts (highlighted with the arrows), while after 3 hours, the peptide signal was detected within the cytoplasm of the fibroblasts (Figure 7A (ii)). Then, the internalization was further confirmed to occur via binding with the PDGFRα receptor. Both peptides were incubated with untreated fibroblasts and fibroblasts treated with an siRNA designed to downregulate PDGFRα expression (Figure 7B). As shown in Figure 7B, the uptake of peptides was significantly reduced in cells with downregulated PDGFRα receptors, thus confirming the mechanism of peptide entry. Once inside the cells, these peptides are entrapped within the endosomes. To study their ability to escape from these endosomes, staining with LysoBrite was performed. LysoBrite is a fluorescent dye that selectively stains lysosomes. As shown in Figure 8, peptide 5 exhibited no colocalization with the lysosome marker, whereas peptide 3 showed only partial colocalization. This suggests that these peptides are not degraded in the lysosomes but are capable of effectively escaping from the endosomes (Figure 11). After confirming the ability of these peptides to preferentially internalize into fibroblasts through binding with the PDGFRα receptor and their ability to escape from the endosomes, peptide 3 and peptide 5 were further studied in conjugation with antisense oligonucleotide sequences (ASOs) capable of correcting the common deep intronic mutation (c.930+189C>T) in the COL6A1 gene (Bolduc et al., 2019; Aguti et al., 2020). The original sequences of both peptides and slightly modified sequences of peptide 3 were utilized in conjugation with ASOs in 2’-O- methoxyethyl (2’-MOE) backbone and phosphorodiamidate morpholino oligomer (PMO) chemistries. The orientations of the peptides and oligos, as well as their sequences, are listed in table 2 below: Table 2: List of compounds synthetized. ID Peptide seq ASO seq ASO Orientation Linke Conjugation comp chemistr of r chemistry ound y conjugatio n Pep3 N ter- 5'- ) - RSQVDPTSAN 2’-MOE C-ter pep^de SMC Direct coupling (S FL AGATGGAGGGG IWPPSVEVKRC- ACGGCGAGG-3 +5' end ASO C between 5’ amino MOE- C ter modifier C6 and - 5/6 (SEQ ID NO: 33) (SEQ ID NO: 35) SH group in cysteine Pep-3 N ter- 5'- RRRRRRSQVDP AGATGGAG 2’-MOE C-ter pep^de SMC Direct coupling (+R) - GGG TSANFLIWPPC-C ACGGCGAGG-3 +5' end ASO C between 5’ amino MOE- ter modifier C6 and - 5/6 (SEQ ID NO: 34) (SEQ ID NO: 35) SH group in cysteine Pep3- N ter- 5’- RSQVDPTSANFL GTGGCTGTC PMO N-ter No Copper free click PMO9 CTT IWPPCVEVKR-C GTCCTTCCAGAT pep^de + 3' linker chemistry ter G-3’ end ASO (SEQ ID NO: 4) (SEQ ID NO: 36) Pep5- N ter- 5’- KRCTGCCNTSS GTGGCTG PMO N-ter No Copper free click PMO9 TCCTT VKCQPSRVHHR- GTCCTTCCAGAT pep^de + 3' linker chemistry C ter G-3’ end ASO (SEQ ID NO: 6) (SEQ ID NO: 36) All four compounds were tested in patient's skin fibroblasts using gymnotic delivery, and their efficiency was compared with naked ASOs (MOE-5/6 and PMO9). As shown in Figure 9, Pep3 (S)-MOE5/6, compared to the naked ASO (MOE-5/6), was unable to reduce the expression of the mutant transcript when tested via gymnotic delivery, but it exhibited comparable efficiency when tested using lipofectamine 2000 as a transfection reagent. This suggests a potential inefficiency of endosomal escape of peptide 3(S) which was confirmed using the LysoBrite staining that showed a colocalization of peptide 3(S) with the lysosome marker (Figure 9C). Based on this observation, five arginine residues were added at the N-terminus of peptide 3 (Pep3 (+R)-MOE5/6) to enhance endosomal escape. As seen in Figure 9D, the introduction of positively charged amino acids significantly improved the compound's efficiency, demonstrating enhanced efficiency compared to the naked ASO in reducing the mutant transcript expression. When peptide 3 and peptide 5 were conjugated with a PMO oligo and tested at high concentrations (5 or 10 µM), they exhibited similar efficiency compared to naked ASO (PMO9) (data not shown). However, at lower concentrations (200 nM and 500 nM), they showed slightly improved efficiency in reducing mutant transcript expression. This improvement was predominantly observed when the PMO oligo was conjugated with peptide 3 (Figure 10). In contrast to the results observed with naked PMO9, Pep3-PMO9 showed a significant reduction in mutant transcripts at both concentrations. Furthermore, the cytotoxicity of each compound was tested in patient's skin fibroblasts, demonstrating no signs of toxicity. (Figure 10C). Table 3 – Peptide ligands and encoding nucleic acid sequences Ligand Peptide Peptide sequence Nucleic Nucleic acid sequence SEQ ID acid SEQ No. ID No. 2 SIEEAVPAVCKTR 15 AGCATCGAGGAAGCTGTCCCCG TVIYEIPRS CTGTCTGCAAGACCAGGACGGT CATTTACGAGATTCCTCGGAGT 3 KTRTVIYEIPRSQV 16 AAGACCAGGACGGTCATTTACG DPTSANFL AGATTCCTCGGAGTCAGGTCGA CCCCACGTCCGCCAACTTCCTG 4 RSQVDPTSANFLI 17 CGGAGTCAGGTCGACCCCACGT WPPCVEVKR CCGCCAACTTCCTGATCTGGCC CCCGTGCGTGGAGGTGAAACG C 5 FLIWPPCVEVKRC 18 TTCCTGATCTGGCCCCCGTGCG TGCCNTSSV TGGAGGTGAAACGCTGCACCG GCTGCTGCAACACGAGCAGTGT C 6 KRCTGCCNTSSV 19 AAACGCTGCACCGGCTGCTGCA KCQPSRVHHR ACACGAGCAGTGTCAAGTGCCA GCCCTCCCGCGTCCACCACCG C 7 SVKCQPSRVHHR 20 AGTGTCAAGTGCCAGCCCTCCC SVKVAKVEYV GCGTCCACCACCGCAGCGTCAA GGTGGCCAAGGTGGAATACGTC 8 HRSVKVAKVEYV 21 CACCGCAGCGTCAAGGTGGCC RKKPKLKEVQ AAGGTGGAATACGTCAGGAAGA AGCCAAAATTAAAAGAAGTCCAG 9 YVRKKPKLKEVQ 22 TACGTCAGGAAGAAGCCAAAAT VRLEEHLECA TAAAAGAAGTCCAGGTGAGGTT AGAGGAGCATTTGGAGTGCGCC 10 VQVRLEEHLECA 23 GTCCAGGTGAGGTTAGAGGAGC CATTSLNPDY ATTTGGAGTGCGCCTGCGCGAC CACAAGCCTGAATCCGGATTAT 11 CACATTSLNPDYR 24 TGCGCCTGCGCGACCACAAGC EEDTGRPRE CTGAATCCGGATTATCGGGAAG AGGACACGGGAAGGCCTAGGG AG 12 DYREEDTGRPRE 25 GATTATCGGGAAGAGGACACGG SGKKRKRKRL GAAGGCCTAGGGAGTCAGGTAA AAAACGGAAAAGAAAAAGGTTA 13 EEDTGRPRESGK 26 GAAGAGGACACGGGAAGGCCT KRKRKRLKPT AGGGAGTCAGGTAAAAAACGGA AAAGAAAAAGGTTAAAACCCAC C 14 QVDPTSANFLIWP 27 CAGGTCGACCCCACGTCCGCCA PC ACTTCCTGATCTGGCCCCCGTG C Pep-3 33 RSQVDPTSANFLI (S) WPPSVEVKRC Pep- 34 RRRRRRSQVDPT 3(+R) SANFLIWPPC Sequences SEQ ID NO: 1 (125 aa ligand sequence with binding affinity to PDGFRα) SIEEAVPAVCKTRTVIYEIPRSQVDPTSANFLIWPPCVEVKRCTGCCNTSSVKCQPSRVHHR SVKVAKVEYVRKKPKLKEVQVRLEEHLECACATTSLNPDYREEDTGRPRESGKKRKRKRLK PT SEQ ID NO: 28 (PDGFA). Underlined region is the 125 aa ligand sequence with binding affinity to PDGFRα MRTLACLLLLGCGYLAHVLAEEAEIPREVIERLARSQIHSIRDLQRLLEIDSVGSEDSLDTSLRAHGVHATKHVP EKRPLPIRRKRSIEEAVPAVCKTRTVIYEIPRSQVDPTSANFLIWPPCVEVKRCTGCCNTSSVKCQPSRVHHRSV KVAKVEYVRKKPKLKEVQVRLEEHLECACATTSLNPDYREEDTGRPRESGKKRKRKRLKPT SEQ ID NO: 29 (PDGFA). ATGAGGACCTTGGCTTGCCTGCTGCTCCTCGGCTGCGGATACCTCGCCCATGTTCTGGCCGAGGAAGCCG AGATCCCCCGCGAGGTGATCGAGAGGCTGGCCCGCAGTCAGATCCACAGCATCCGGGACCTCCAGCGACT CCTGGAGATAGACTCCGTAGGGAGTGAGGATTCTTTGGACACCAGCCTGAGAGCTCACGGGGTCCATGCC ACTAAGCATGTGCCCGAGAAGCGGCCCCTGCCCATTCGGAGGAAGAGAAGCATCGAGGAAGCTGTCCCCG CTGTCTGCAAGACCAGGACGGTCATTTACGAGATTCCTCGGAGTCAGGTCGACCCCACGTCCGCCAACTT CCTGATCTGGCCCCCGTGCGTGGAGGTGAAACGCTGCACCGGCTGCTGCAACACGAGCAGTGTCAAGTGC CAGCCCTCCCGCGTCCACCACCGCAGCGTCAAGGTGGCCAAGGTGGAATACGTCAGGAAGAAGCCAAAAT TAAAAGAAGTCCAGGTGAGGTTAGAGGAGCATTTGGAGTGCGCCTGCGCGACCACAAGCCTGAATCCGGA TTATCGGGAAGAGGACACGGGAAGGCCTAGGGAGTCAGGTAAAAAACGGAAAAGAAAAAGGTTAAAACCC ACCTAA SEQ ID NO: 30 (PDGFRalpha). Underlined is the canonical binding region for PDGFA MGTSHPAFLVLGCLLTGLSLILCQLSLPSILPNENEKVVQLNSSFSLRCFGESEVSWQYP MSEEESSDVEIRNEENNSGLFVTVLEVSSASAAHTGLYTCYYNHTQTEENELEGRHIYIY VPDPDVAFVPLGMTDYLVIVEDDDSAIIPCRTTDPETPVTLHNSEGVVPASYDSRQGFNG TFTVGPYICEATVKGKKFQTIPFNVYALKATSELDLEMEALKTVYKSGETIVVTCAVFNN EVVDLQWTYPGEVKGKGITMLEEIKVPSIKLVYTLTVPEATVKDSGDYECAARQATREVK EMKKVTISVHEKGFIEIKPTFSQLEAVNLHEVKHFVVEVRAYPPPRISWLKNNLTLIENL TEITTDVEKIQEIRYRSKLKLIRAKEEDSGHYTIVAQNEDAVKSYTFELLTQVPSSILDL VDDHHGSTGGQTVRCTAEGTPLPDIEWMICKDIKKCNNETSWTILANNVSNIITEIHSRD RSTVEGRVTFAKVEETIAVRCLAKNLLGAENRELKLVAPTLRSELTVAAAVLVLLVIVII SLIVLVVIWKQKPRYEIRWRVIESISPDGHEYIYVDPMQLPYDSRWEFPRDGLVLGRVLG SGAFGKVVEGTAYGLSRSQPVMKVAVKMLKPTARSSEKQALMSELKIMTHLGPHLNIVNL LGACTKSGPIYIITEYCFYGDLVNYLHKNRDSFLSHHPEKPKKELDIFGLNPADESTRSY VILSFENNGDYMDMKQADTTQYVPMLERKEVSKYSDIQRSLYDRPASYKKKSMLDSEVKN LLSDDNSEGLTLLDLLSFTYQVARGMEFLASKNCVHRDLAARNVLLAQGKIVKICDFGLA RDIMHDSNYVSKGSTFLPVKWMAPESIFDNLYTTLSDVWSYGILLWEIFSLGGTPYPGMM VDSTFYNKIKSGYRMAKPDHATSEVYEIMVKCWNSEPEKRPSFYHLSEIVENLLPGQYKK SYEKIHLDFLKSDHPAVARMRVDSDNAYIGVTYKNEEDKLKDWEGGLDEQRLSADSGYII PLPDIDPVPEEEDLGKRNRHSSQTSEESAIETGSSSSTFIKREDETIEDIDMMDDIGIDS SDLVEDSFL SEQ ID NO: 31. PDGFRalpha canonical binding region for PDGFA IYIYVPDPDVAFVPLGMTDYLVIVEDDDSAIIPCRTTDPETPVTLHNSEGVVPASYDSRQGFNG TFTVGPYICEATVKGKKFQTI SEQ ID NO: 32. PDGFRalpha nucleotide sequence ATGGGGACTTCCCATCCGGCGTTCCTGGTCTTAGGCTGTCTTCTCACAGGGCTGAGCCTAATCCTCTGCC AGCTTTCATTACCCTCTATCCTTCCAAATGAAAATGAAAAGGTTGTGCAGCTGAATTCATCCTTTTCTCT GAGATGCTTTGGGGAGAGTGAAGTGAGCTGGCAGTACCCCATGTCTGAAGAAGAGAGCTCCGATGTGGAA ATCAGAAATGAAGAAAACAACAGCGGCCTTTTTGTGACGGTCTTGGAAGTGAGCAGTGCCTCGGCGGCCC ACACAGGGTTGTACACTTGCTATTACAACCACACTCAGACAGAAGAGAATGAGCTTGAAGGCAGGCACAT TTACATCTATGTGCCAGACCCAGATGTAGCCTTTGTACCTCTAGGAATGACGGATTATTTAGTCATCGTG GAGGATGATGATTCTGCCATTATACCTTGTCGCACAACTGATCCCGAGACTCCTGTAACCTTACACAACA GTGAGGGGGTGGTACCTGCCTCCTACGACAGCAGACAGGGCTTTAATGGGACCTTCACTGTAGGGCCCTA TATCTGTGAGGCCACCGTCAAAGGAAAGAAGTTCCAGACCATCCCATTTAATGTTTATGCTTTAAAAGCA ACATCAGAGCTGGATCTAGAAATGGAAGCTCTTAAAACCGTGTATAAGTCAGGGGAAACGATTGTGGTCA CCTGTGCTGTTTTTAACAATGAGGTGGTTGACCTTCAATGGACTTACCCTGGAGAAGTGAAAGGCAAAGG CATCACAATGCTGGAAGAAATCAAAGTCCCATCCATCAAATTGGTGTACACTTTGACGGTCCCCGAGGCC ACGGTGAAAGACAGTGGAGATTACGAATGTGCTGCCCGCCAGGCTACCAGGGAGGTCAAAGAAATGAAGA AAGTCACTATTTCTGTCCATGAGAAAGGTTTCATTGAAATCAAACCCACCTTCAGCCAGTTGGAAGCTGT CAACCTGCATGAAGTCAAACATTTTGTTGTAGAGGTGCGGGCCTACCCACCTCCCAGGATATCCTGGCTG AAAAACAATCTGACTCTGATTGAAAATCTCACTGAGATCACCACTGATGTGGAAAAGATTCAGGAAATAA GGTATCGAAGCAAATTAAAGCTGATCCGTGCTAAGGAAGAAGACAGTGGCCATTATACTATTGTAGCTCA AAATGAAGATGCTGTGAAGAGCTATACTTTTGAACTGTTAACTCAAGTTCCTTCATCCATTCTGGACTTG GTCGATGATCACCATGGCTCAACTGGGGGACAGACGGTGAGGTGCACAGCTGAAGGCACGCCGCTTCCTG ATATTGAGTGGATGATATGCAAAGATATTAAGAAATGTAATAATGAAACTTCCTGGACTATTTTGGCCAA CAATGTCTCAAACATCATCACGGAGATCCACTCCCGAGACAGGAGTACCGTGGAGGGCCGTGTGACTTTC GCCAAAGTGGAGGAGACCATCGCCGTGCGATGCCTGGCTAAGAATCTCCTTGGAGCTGAGAACCGAGAGC TGAAGCTGGTGGCTCCCACCCTGCGTTCTGAACTCACGGTGGCTGCTGCAGTCCTGGTGCTGTTGGTGAT TGTGATCATCTCACTTATTGTCCTGGTTGTCATTTGGAAACAGAAACCGAGGTATGAAATTCGCTGGAGG GTCATTGAATCAATCAGCCCAGATGGACATGAATATATTTATGTGGACCCGATGCAGCTGCCTTATGACT CAAGATGGGAGTTTCCAAGAGATGGACTAGTGCTTGGTCGGGTCTTGGGGTCTGGAGCGTTTGGGAAGGT GGTTGAAGGAACAGCCTATGGATTAAGCCGGTCCCAACCTGTCATGAAAGTTGCAGTGAAGATGCTAAAA CCCACGGCCAGATCCAGTGAAAAACAAGCTCTCATGTCTGAACTGAAGATAATGACTCACCTGGGGCCAC ATTTGAACATTGTAAACTTGCTGGGAGCCTGCACCAAGTCAGGCCCCATTTACATCATCACAGAGTATTG CTTCTATGGAGATTTGGTCAACTATTTGCATAAGAATAGGGATAGCTTCCTGAGCCACCACCCAGAGAAG CCAAAGAAAGAGCTGGATATCTTTGGATTGAACCCTGCTGATGAAAGCACACGGAGCTATGTTATTTTAT CTTTTGAAAACAATGGTGACTACATGGACATGAAGCAGGCTGATACTACACAGTATGTCCCCATGCTAGA AAGGAAAGAGGTTTCTAAATATTCCGACATCCAGAGATCACTCTATGATCGTCCAGCCTCATATAAGAAG AAATCTATGTTAGACTCAGAAGTCAAAAACCTCCTTTCAGATGATAACTCAGAAGGCCTTACTTTATTGG ATTTGTTGAGCTTCACCTATCAAGTTGCCCGAGGAATGGAGTTTTTGGCTTCAAAAAATTGTGTCCACCG TGATCTGGCTGCTCGCAACGTCCTCCTGGCACAAGGAAAAATTGTGAAGATCTGTGACTTTGGCCTGGCC AGAGACATCATGCATGATTCGAACTATGTGTCGAAAGGCAGTACCTTTCTGCCCGTGAAGTGGATGGCTC CTGAGAGCATCTTTGACAACCTCTACACCACACTGAGTGATGTCTGGTCTTATGGCATTCTGCTCTGGGA GATCTTTTCCCTTGGTGGCACCCCTTACCCCGGCATGATGGTGGATTCTACTTTCTACAATAAGATCAAG AGTGGGTACCGGATGGCCAAGCCTGACCACGCTACCAGTGAAGTCTACGAGATCATGGTGAAATGCTGGA ACAGTGAGCCGGAGAAGAGACCCTCCTTTTACCACCTGAGTGAGATTGTGGAGAATCTGCTGCCTGGACA ATATAAAAAGAGTTATGAAAAAATTCACCTGGACTTCCTGAAGAGTGACCATCCTGCTGTGGCACGCATG CGTGTGGACTCAGACAATGCATACATTGGTGTCACCTACAAAAACGAGGAAGACAAGCTGAAGGACTGGG AGGGTGGTCTGGATGAGCAGAGACTGAGCGCTGACAGTGGCTACATCATTCCTCTGCCTGACATTGACCC TGTCCCTGAGGAGGAGGACCTGGGCAAGAGGAACAGACACAGCTCGCAGACCTCTGAAGAGAGTGCCATT GAGACGGGTTCCAGCAGTTCCACCTTCATCAAGAGAGAGGACGAGACCATTGAAGACATCGACATGATGG ATGACATCGGCATAGACTCTTCAGACCTGGTGGAAGACAGCTTCCTGTAA

Claims

Claims 1. A peptide ligand that binds to an extracellular or transmembrane region of PDGFR- alpha, wherein the peptide ligand comprises SEQ ID NO: 4 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 3 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 2 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 5 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 6 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprising SEQ ID NO: 7 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 8 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 9 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 10 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 11 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 12 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 13 or a peptide ligand sequence having at least 80% homology thereto; a peptide ligand comprises SEQ ID NO: 14 or a peptide ligand sequence having at least 80% homology thereto.

2. The peptide ligand of claim 1, wherein the N-terminus and/or C-terminus comprises at least one positively charged residue.

3. The peptide ligand of claim 1, wherein the peptide ligand comprises the amino acid sequence of SEQ ID NO: 1, or an amino acid sequence with at least 80% homology thereto.

4. The peptide ligand of any of the preceding claims, wherein the extracellular or transmembrane region of PDGFR-alpha is expressed by fibroblasts.

5. The peptide ligand of any of the preceding claims, wherein the peptide ligand binds podocytes, and/or cells originating from tissues selected from list of liver, kidney, neural and/or endothelium.

6. The peptide ligand of any of the preceding claims, wherein the peptide ligand is internalised upon binding to the extracellular or transmembrane region of PDGFR- alpha.

7. The peptide ligand of any of the preceding claims, further comprising an additional moiety.

8. The peptide ligand of claim 7, wherein said additional moiety is selected from a toxin, enzyme, radioisotope, half-life extending moiety, label, therapeutic molecule or other chemical moiety.

9. The peptide ligand of claim 8, wherein said therapeutic molecule is an RNA or DNA oligonucleotide.

10. The peptide ligand of claim 9, wherein said RNA or DNA oligonucleotide is an ASO, siRNA or saRNA.

11. A pharmaceutical composition comprising a peptide ligand according to any of the preceding claims and optionally a pharmaceutically acceptable carrier.

12. A method for treating a cancer, an immune disorder, a respiratory disorder, metabolic disorder, inflammatory disorder, allergy, transplant rejection, viral infection, muscular dystrophy and/or neuromuscular disease, immune deficiency, and other immune system-related disorder comprising administering a therapeutically effective amount of a peptide ligand according to any of claims 1 to 10 or a pharmaceutical composition according to claim 11.

13. Use of a peptide ligand according to any of claims 1 to 10 or a pharmaceutical composition according to claim 11 in the manufacture of a medicament for the treatment of a cancer, an immune disorder, a respiratory disorder, metabolic disorder, inflammatory disorder, allergy, transplant rejection, viral infection, muscular dystrophy and/or neuromuscular disease, immune deficiency, and other immune system-related disorder.

14. A peptide ligand according to any of claims 1 to 10 or a pharmaceutical composition according to claim 11 for use as a treatment.

15. A peptide ligand according to any of claims 1 to 10 or a pharmaceutical composition according to claim 11 for use as a treatment for cancer, an immune disorder, a respiratory disorder, metabolic disorder, inflammatory disorder, allergy, transplant rejection, viral infection, muscular dystrophy and/or neuromuscular disease, immune deficiency, and other immune system-related disorder.

16. A method according to claim 12, a use according to claim 13 or a peptide ligand or a pharmaceutical composition according to claim 15, wherein the muscular dystrophy is selected from a congenital muscular dystrophy or myopathy, Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb- girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, tibial muscular dystrophy, distal muscular dystrophy, and Emery-Dreifuss muscular dystrophy.

17. A method according to claim 12, a use according to claim 13 or a peptide ligand or a pharmaceutical composition according to claim 15, wherein fibrosis is targeted in the muscular dystrophy selected from a congenital muscular dystrophy or myopathy, Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, tibial muscular dystrophy, distal muscular dystrophy, and Emery-Dreifuss muscular dystrophy.

18. A method according to claim 12, a use according to claim 13 or a peptide ligand or a pharmaceutical composition according to claim 15, wherein the muscular dystrophy is a congenital muscular dystrophy or myopathy, wherein the congenital muscular dystrophy or myopathy resulting from mutations in any of the three collagen VI genes (COL6A1, COL6A2, COL6A3), clinically known as Ullrich congenital muscular dystrophy or Bethlem myopathy and intermediate clinical manifestations.

19. A method according to claim 12, a use according to claim 13 or a peptide ligand or a pharmaceutical composition according to claim 15, wherein said cancer is selected from bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, cutaneous or intraocular malignant melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, breast cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, kidney cancer, sarcoma of soft tissue, cancer of the urethra, cancer of the bladder, renal cancer, lung cancer, non-small cell lung cancer, thymoma, urothelial carcinoma leukemia, prostate cancer, mesothelioma, adrenocortical carcinoma, lymphomas, such as such as Hodgkin's disease, non-Hodgkin's, gastric cancer, and multiple myelomas.

20. A nucleic acid molecule comprising a nucleotide sequence encoding a peptide ligand according to any of claims 1 to 10.

21. A nucleic acid molecule comprising a nucleotide sequence encoding a peptide ligand according to claim 20 selected from SEQ ID NO: 15 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 16 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 17 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 18 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 19 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 20 or a nucleotide having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 21 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 22 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 23 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 24 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 25 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 26 or a nucleotide sequence having at least 80% homology thereto; a nucleotide comprising SEQ ID NO: 27 or a nucleotide sequence having at least 80% homology thereto.

22. The nucleic acid molecule according to claim 21, wherein the N-terminus and/or C- terminus additionally comprises nucleotides encoding at least one positively charged residue.

23. A vector comprising a nucleic acid according to any one of claims 20 to 22.

24. A host cell comprising a nucleic acid according to any one of claims 20 to 22 or a vector according to claim 23.

25. A host cell according to claim 24 wherein said host cell is a bacterial, yeast, insect, plant, viral or mammalian cell.

26. A method for producing the peptide ligand of any of claims 1 to 10 comprising a nucleic acid encoding said peptide ligand in a host cell and isolating the peptide ligand from the host cell.

27. A system to identify peptide ligand sequences which can specifically bind to PDGFR- alpha for drug delivery, comprising the steps of identifying a cell-surface epitope, design of peptide ligand sequence capable of binding at the PDGF-A-PDGFR-alpha interface, and uptake and/or internalisation of the peptide ligand by the host cell.

28. A multimeric binding complex comprising at least two of the peptide ligands according to any one of claims 1 to 15.

29. The multimeric binding complex of claim 28 further comprising an additional moiety.

30. The multimeric binding complex of claim 29, wherein said additional moiety is selected from a toxin, enzyme, radioisotope, half-life extending moiety, label, therapeutic molecule or other chemical moiety.

31. The multimeric binding complex of claim 30, wherein said therapeutic molecule is an RNA or DNA oligonucleotide.

32. The multimeric binding complex of claim 31, where said RNA or DNA oligonucleotide is an ASO, siRNA or saRNA.

33. A tissue delivery complex which comprises a peptide ligand according to claims 1 to 15 or a multimeric binding complex according to claims 28 to 32.

34. The tissue delivery complex according to claim 33, wherein the tissue delivery complex is a muscle tissue delivery complex.

35. The tissue delivery complex according to claim 33, wherein the tissue delivery complex is a liver, kidney and/or endothelium delivery complex.

36. The tissue delivery complex according to claims 33 to 35 for use in the treatment of muscular dystrophy and/or diseases of the liver, kidney and/or endothelium.

37. The tissue delivery complex according to claim 36 wherein the muscular dystrophy is selected from a congenital muscular dystrophy or myopathy, Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb- girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, tibial muscular dystrophy, distal muscular dystrophy, and Emery-Dreifuss muscular dystrophy.

38. The tissue delivery complex according to claim 36 wherein fibrosis is targeted in the muscular dystrophy selected from a congenital muscular dystrophy or myopathy, Duchenne muscular dystrophy, Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, tibial muscular dystrophy, distal muscular dystrophy, and Emery-Dreifuss muscular dystrophy.

39. The tissue delivery complex according to claim 37, wherein the muscular dystrophy is a congenital muscular dystrophy or myopathy resulting from mutations in any of the three collagen VI genes (COL6A1, COL6A2, COL6A3), clinically known as Ullrich congenital muscular dystrophy or Bethlem myopathy and intermediate clinical manifestations.

40. A method of modifying the expression of a target gene in a fibroblast and/or cells originating from tissues selected from list of liver, kidney, skeletal muscle and/or endothelium comprising providing to the cell an RNA or DNA oligonucleotide conjugated to a peptide ligand according to any of claims 1 to 10.

41. The method of claim 39 wherein the RNA or DNA oligonucleotide is an ASO, siRNA or saRNA.

42. A kit comprising the peptide ligand according to any of claims 1 to 10 or a pharmaceutical composition according to claim 11 and optionally instructions for use.

43. A therapeutic molecule comprising the peptide ligand of claims 1 to 10.

44. The therapeutic molecule of claim 43 wherein the therapeutic molecule is an RNA or DNA oligonucleotide.

45. The therapeutic molecule of claim 44 wherein the RNA or DNA oligonucleotide is an ASO, siRNA or saRNA.

46. A method of delivering to a fibroblast and/or podocyte and/or cells originating from tissues selected from list of liver, kidney, skeletal muscle, neural and/or endothelium the peptide ligand of claims 1 to 10, the pharmaceutical composition of claim 11, or the therapeutic molecule of claims 43 to 45.

47. A method of screening for a peptide ligand of claim 1.

48. The method of claim 47, comprising analysing a first single-cell RNA sequencing dataset of a first cell population to identify genes encoding cell surface proteins from the first cell population and/or analysing a surfaceome dataset of said first cell population to identify cell-surface proteins from the first cell population, comparing the first single-cell RNA sequencing and/or surfaceome dataset(s) to a second dataset, and excluding the cell surface proteins highly expressed in liver and/or kidneys.

49. The method of claim 48, comprising the identification of a target that is specifically or more abundantly expressed in the first cell population.

50. A method for targeting fibroblasts comprising administering a peptide ligand according to any of claims 1 to 10 or a pharmaceutical composition according to claim 11, wherein the peptide ligand targets an extracellular or transmembrane region of PDGFR-alpha.

51. A method for targeting podocytes and/or cells originating from tissues selected from list of liver, kidney, skeletal muscle, neural and/or endothelium comprising administering a peptide ligand according to any of claims 1 to 10 or a pharmaceutical composition according to claim 11.