Jingfen Han1, Jia Cai1, Wuyinga Borjihan1, Tsogzolmaa Ganbold1, Tariq M Rana2, Huricha Baigude3. 1. School of Chemistry & Chemical Engineering, Inner Mongolia University, 235 West College Road, Hohhot, Inner Mongolia, 010020, PR China. 2. Program for RNA Biology, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; Department of Pediatrics, Rady Children's Hospital San Diego and University of California San Diego, La Jolla, CA 92093, USA. Electronic address: trana@sanfordburnham.org. 3. School of Chemistry & Chemical Engineering, Inner Mongolia University, 235 West College Road, Hohhot, Inner Mongolia, 010020, PR China; Program for RNA Biology, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: hbaigude@imu.edu.cn.
Abstract
RNA interference (RNAi) down-regulates gene expression post-transcriptionally, which is a therapeutically significant phenomenon that could potentially reduce the level of disease related proteins that are undruggable by conventional small molecular approaches. However, clinical application of small interference RNAs (siRNAs) requires design of potent siRNA sequences and development of safe and efficient delivery systems. To create a biocompatible siRNA delivery agent, we chemically modified natural polysaccharide curdlan in a regioselective manner to introduce amino group in the glucose units. The resulting 6-amino-curdlan (6AC) is water soluble and forms nanoparticles upon complexing with siRNAs. The novel curdlan-based nanoparticles efficiently delivered siRNAs to human cancer cells and mouse primary cells, and reduced 70-90% of target mRNA level. Moreover, 6AC nanoparticles delivered siRNA targeting eGFP to mouse embryonic stem (mES) cells stably expressing eGFP, and produced substantial reductions of GFP protein level. The novel curdlan-based nanoparticle is a promising vehicle for delivery of short RNAs to knock down endogenous mRNAs.
RNA interference (RNAi) down-regulates gene expression post-transcriptionally, which is a therapeutically significant phenomenon that could potentially reduce the level of disease related proteins that are undruggable by conventional small molecular approaches. However, clinical application of small interference RNAs (siRNAs) requires design of potent siRNA sequences and development of safe and efficient delivery systems. To create a biocompatible siRNA delivery agent, we chemically modified natural polysacchariden>an class="Chemical">curdlan in a regioselective manner to introduce amino group in the glucose units. The resulting 6-amino-curdlan (6AC) is water soluble and forms nanoparticles upon complexing with siRNAs. The novel curdlan-based nanoparticles efficiently delivered siRNAs to humancancer cells and mouse primary cells, and reduced 70-90% of target mRNA level. Moreover, 6AC nanoparticles delivered siRNA targeting eGFP to mouse embryonic stem (mES) cells stably expressing eGFP, and produced substantial reductions of GFP protein level. The novel curdlan-based nanoparticle is a promising vehicle for delivery of short RNAs to knock down endogenous mRNAs.
Authors: Kevin T Love; Kerry P Mahon; Christopher G Levins; Kathryn A Whitehead; William Querbes; J Robert Dorkin; June Qin; William Cantley; Liu Liang Qin; Timothy Racie; Maria Frank-Kamenetsky; Ka Ning Yip; Rene Alvarez; Dinah W Y Sah; Antonin de Fougerolles; Kevin Fitzgerald; Victor Koteliansky; Akin Akinc; Robert Langer; Daniel G Anderson Journal: Proc Natl Acad Sci U S A Date: 2010-01-11 Impact factor: 11.205
Authors: Jürgen Soutschek; Akin Akinc; Birgit Bramlage; Klaus Charisse; Rainer Constien; Mary Donoghue; Sayda Elbashir; Anke Geick; Philipp Hadwiger; Jens Harborth; Matthias John; Venkitasamy Kesavan; Gary Lavine; Rajendra K Pandey; Timothy Racie; Kallanthottathil G Rajeev; Ingo Röhl; Ivanka Toudjarska; Gang Wang; Silvio Wuschko; David Bumcrot; Victor Koteliansky; Stefan Limmer; Muthiah Manoharan; Hans-Peter Vornlocher Journal: Nature Date: 2004-11-11 Impact factor: 49.962
Authors: Mark E Davis; Jonathan E Zuckerman; Chung Hang J Choi; David Seligson; Anthony Tolcher; Christopher A Alabi; Yun Yen; Jeremy D Heidel; Antoni Ribas Journal: Nature Date: 2010-03-21 Impact factor: 49.962
Authors: Myriam Aouadi; Gregory J Tesz; Sarah M Nicoloro; Mengxi Wang; My Chouinard; Ernesto Soto; Gary R Ostroff; Michael P Czech Journal: Nature Date: 2009-04-30 Impact factor: 49.962
Authors: Jeongyun Heo; Thomas A Sobiech; Hilliard L Kutscher; Lee Chaves; Dinesh K Sukumaran; Shanta Karki; Admire Dube; Paras N Prasad; Jessica L Reynolds Journal: Macromol Biosci Date: 2020-12-07 Impact factor: 4.979