nanobiotechnology-2018-posters-abstracts

Nanobiotechnology 2018

Page 57

Nano Research & Applications

ISSN: 2471-9838

E u r o S c i C o n C o n f e r e n c e o n

Nanotech & Nanobiotechnology

J u l y 1 2 - 1 3 , 2 0 1 8

P a r i s , F r a n c e

mall interfering (si) RNAs can be used to silence disease-causing genes. However, their development as drugs has been limited

mainly in knocking down liver gene expression, since delivery to other tissues requires development of a targeted delivery

carrier. Modulating immune cells function using siRNAs holds great promise in advancing targeted therapies to many immune-

related disorders including cancer, inflammation, autoimmunity, and viral infections. However, the ability to effectively knockdown

gene expression in leukocytes is still challenging. Here, we present a modular platform to target specifc cell types, exemplifed

here with immune cells, using siRNA loaded lipid nanoparticles (LNP) coated with oriented, targeting antibodies noncovalently

bound to a membrane-anchored lipoprotein that recognizes their Fc domain. Unlike chemically conjugated antibodies, these

oriented antibodies maintain their high affnity and the LNPs avoid scavenging by Fc receptors on macrophages. A simple switch

in 5 different targeting antibodies (against Ly6C, CD3, CD4, CD25 and Itgb7) redirected the LNP for exquisitely specifc uptake in

diverse leukocyte subsets

in vivo

and enabled specifc knockdown in diffcult-to-transfect CD4

cells. Intravenously injected anti-

Ly6C-coated LNP encapsulating TNF siRNAs were taken up selectively by Ly6C

monocytes and activated tissue macrophages,

suppressed TNF-α expression in the colon and ameliorated inflammatory bowel disease symptoms in a DSS-induced colitis

mouse model, demonstrating the platform’s potential therapeutic utility. This approach opens new avenues for studying cell

biology

in vivo

and potentially for a wide range of therapeutic applications in a cell-specifc manner.

A modular platform for targeted RNAi therapeutics

using biologically-lipidated antibodies

Itai Benhar, Ranit Kedmi, Nuphar Veiga, Limor Nahary, Edo Kon, Meir

Goldsmith, Dan Rosenblum, Shani Leviatan-Ben-Arye and Dan Peer

Tel Aviv University, Israel

Nano Res Appl 2018, Volume 4

DOI: 10.21767/2471-9838-C2-012