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Transcript
Poster No. 32
Title:
Cell Penetrating Peptide for Delivery of DNA, siRNA and Quantum Dots in vitro and in vivo
Authors:
Leslie Johnson, Siobhan Cashman, Rajendra Kumar-Singh
Presented by:
Leslie Johnson
Department(s):
Department of Ophthalmology, Tufts University School of Medicine
Abstract:
Delivery of DNA, siRNA and drugs into cells is hampered by inefficient penetration across the plasma
membrane. We describe a novel cell penetrating peptide (POD) capable of being chemically or electrostatically
conjugated to small and/or large molecules and ferry those molecules into the cytoplasm of cells in vitro or
in vivo without causing disruption of the plasma membrane. Fluorescently-labeled POD enters the cells and was
observed within the cytoplasm within 5 minutes. In addition, POD compacted and delivered plasmid DNA
in vitro, achieving transgene expression in >50% of human embryonic retinoblasts. POD was subsequently used
to deliver siRNA to cells which silenced transgene expression by >50%. POD could also be used to deliver
quantum dots in vitro and in vivo suggesting the peptide is capable of transporting large cargo. Upon ocular
delivery via subretinal and intravitreal injections, fluorescently-labeled POD rapidly entered the neural retina
and localized to retinal pigment epithelium, photoreceptor and ganglion cells. Additionally, POD was able to
enter corneal epithelium, sclera, choroid and optic nerve via topical application to the cornea. Finally, POD
functioned as a bacteriostatic agent, a useful property for a carrier of molecules to post mitotic neural ocular
tissues. Preliminary studies indicate that POD also has cell penetrating properties in vivo in other tissues.
33