Cell-penetrating peptide for enhanced delivery of nucleic acids and drugs to ocular tissues including retina and cornea.
As in other organ systems, gene and drug delivery to ocular tissues such as the retina and cornea is hampered by inefficient penetration of therapeutic molecules across the plasma membrane. We describe the use of a novel peptide for ocular delivery (POD) with protein transduction properties, for delivery of small and large molecules across the plasma membrane. POD enters cells within 5 minutes in a temperature dependent manner. POD can compact and deliver plasmid DNA, achieving transgene expression in >50% of human embryonic retinoblasts. Delivery of small interfering RNA (siRNA) duplexes to cells using POD, allowed for silencing of transgene expression by >50%. POD could also be used to deliver quantum dots in vitro and in vivo. Upon ocular delivery, POD rapidly entered neural retina and localized to retinal pigment epithelium (RPE), photoreceptor, and ganglion cells. Additionally, POD was able to enter corneal epithelium, sclera, choroid, and the dura of the optic nerve via topical application. POD also functions as a bacteriostatic, a useful property for a carrier of molecules to post mitotic neural ocular tissues.
Johnson
Leslie N
LN
Department of Ophthalmology, Tufts University School of Medicine, Boston, Massachusetts, USA.
Cashman
Siobhan M
SM
Kumar-Singh
Rajendra
R
D000595:Amino Acid Sequence; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000235:genetics; D003315:Cornea / Q000378:metabolism*; D003316:Corneal Diseases / Q000188:drug therapy / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage* / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D010957:Plasmids / Q000008:administration & dosage / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage; D012160:Retina / Q000378:metabolism*
D004337:Drug Carriers; D010455:Peptides; D034741:RNA, Small Interfering