title: Non-invasive topical delivery of plasmid DNA to the skin using a peptide carrier.
abstract: Topical delivery to skin is an essential step in non-invasive application of nucleic acid therapeutics for cutaneous disorders. The barrier posed by different layers of the skin - stratum corneum on top followed by the viable epidermis below - makes it extremely challenging for large hydrophilic molecules like nucleic acids to efficiently enter the uncompromised skin. We report an amphipathic peptide Mgpe9 (CRRLRHLRHHYRRRWHRFRC) that can penetrate the uncompromised skin, enter skin cells and deliver plasmid DNA efficiently as nanocomplexes in vitro and in vivo without any additional physical or chemical interventions prevalent currently. We observe efficient gene expression up to the highly proliferating basal layer of the skin without observable adverse reactions or toxic effects after delivery of reporter plasmids. The entry mechanism of nanocomplexes possibly involves reversible modulation of junction proteins accompanied by transient changes in skin structure. This peptide holds potential to be used as an efficient transporter of therapeutic nucleic acids to the skin.
authors.affiliation: Department of Structural Biology, CSIR-Institute of Genomics and Integrative Biology, South Campus, Mathura Road, New Delhi 110020, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110001, India.
authors.forename: Manika
authors.initials: M
authors.lastname: Vij
authors.affiliation: Department of Structural Biology, CSIR-Institute of Genomics and Integrative Biology, South Campus, Mathura Road, New Delhi 110020, India.
authors.forename: Poornemaa
authors.initials: P
authors.lastname: Natarajan
authors.affiliation: Department of Structural Biology, CSIR-Institute of Genomics and Integrative Biology, South Campus, Mathura Road, New Delhi 110020, India.
authors.forename: Bijay Ranjan
authors.initials: BR
authors.lastname: Pattnaik
authors.affiliation: Environmental Carcinogenesis Division, CSIR-Indian Institute of Toxicology Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh 226001, India.
authors.forename: Shamshad
authors.initials: S
authors.lastname: Alam
authors.affiliation: Delhi Technological University, Shahbad Daulatpur, Main Bawana Road, New Delhi 110042, India.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Gupta
authors.affiliation: Delhi Technological University, Shahbad Daulatpur, Main Bawana Road, New Delhi 110042, India.
authors.forename: Deenan
authors.initials: D
authors.lastname: Santhiya
authors.affiliation: Department of Structural Biology, CSIR-Institute of Genomics and Integrative Biology, South Campus, Mathura Road, New Delhi 110020, India.
authors.forename: Rajpal
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Department of Structural Biology, CSIR-Institute of Genomics and Integrative Biology, South Campus, Mathura Road, New Delhi 110020, India.
authors.forename: Archana
authors.initials: A
authors.lastname: Singh
authors.affiliation: Environmental Carcinogenesis Division, CSIR-Indian Institute of Toxicology Research, Post Box No. 80, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh 226001, India.
authors.forename: Kausar M
authors.initials: KM
authors.lastname: Ansari
authors.affiliation: Department of Structural Biology, CSIR-Institute of Genomics and Integrative Biology, South Campus, Mathura Road, New Delhi 110020, India; National Institute of Immunology, New Delhi 110067, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110001, India.
authors.forename: Rajesh S
authors.initials: RS
authors.lastname: Gokhale
authors.affiliation: Department of Structural Biology, CSIR-Institute of Genomics and Integrative Biology, South Campus, Mathura Road, New Delhi 110020, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110001, India.
authors.forename: Vivek T
authors.initials: VT
authors.lastname: Natarajan
authors.affiliation: Department of Structural Biology, CSIR-Institute of Genomics and Integrative Biology, South Campus, Mathura Road, New Delhi 110020, India; Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110001, India. Electronic address: mganguli@igib.res.in.
authors.forename: Munia
authors.initials: M
authors.lastname: Ganguli
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000737:chemistry; D004247:DNA / Q000008:administration & dosage* / Q000737:chemistry; D052816:Foreskin / Q000378:metabolism* / Q000648:ultrastructure; D018014:Gene Transfer Techniques; D006801:Humans; D008297:Male; D008812:Mice, Hairless; D046529:Microscopy, Electron, Transmission; D010539:Permeability; D010957:Plasmids
chemical_list: D057846:Cell-Penetrating Peptides; C000611834:Mgpe9 peptide; D004247:DNA
keywords: Cell penetrating peptide; Dermatology; Nucleic acid delivery; Skin penetration; Topical; Transfection