Improving Small Interfering RNA Delivery In Vivo Through Lipid Conjugation

被引：99

作者：

Osborn, Maire F. ^{[1
]}

Khvorova, Anastasia ^{[1
,2
]}

机构：

[1] Univ Massachusetts, RNA Therapeut Inst, Med Sch, Worcester, MA 01605 USA

[2] Univ Massachusetts, Dept Mol Med, Med Sch, 368 Plantat St, Worcester, MA 01605 USA

来源：

NUCLEIC ACID THERAPEUTICS | 2018年 / 28卷 / 03期

关键词：

siRNA; lipid conjugation; delivery; ANTISENSE OLIGONUCLEOTIDES; MODIFIED SIRNA; GENE; PHOSPHOROTHIOATE; GALNAC; EFFICACY; 5'-VINYLPHOSPHONATE; BIODISTRIBUTION; HUNTINGTIN; POTENCY;

D O I：

10.1089/nat.2018.0725

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

RNA interference (RNAi)-based therapeutics are approaching clinical approval for genetically defined diseases. Current clinical success is a result of significant innovations in the development of chemical architectures that support sustained, multi-month efficacy in vivo following a single administration. Conjugate-mediated delivery has established itself as the most promising platform for safe and targeted small interfering RNA (siRNA) delivery. Lipophilic conjugates represent a major class of modifications that improve siRNA pharmacokinetics and enable efficacy in a broad range of tissues. Here, we review current literature and define key features and limitations of this approach for in vivo modulation of gene expression.

引用

页码：128 / 136

页数：9

共 53 条

[1] Fully 2′-modified oligonucleotide duplexes with improved in vitro potency and stability compared to unmodified small interfering RNA [J].

Allerson, CR ;

Sioufi, N ;

Jarres, R ;

Prakash, TP ;

Naik, N ;

Berdeja, A ;

Wanders, L ;

Griffey, RH ;

Swayze, EE ;

Bhat, B .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (04) :901-904

[2] Hydrophobically Modified siRNAs Silence Huntingtin mRNA in Primary Neurons and Mouse Brain [J].

Alterman, Julia F. ;

Hall, Lauren M. ;

Coles, Andrew H. ;

Hassler, Matthew R. ;

Didiot, Marie-Cecile ;

Chase, Kathryn ;

Abraham, Jasmin ;

Sottosanti, Emily ;

Johnson, Emily ;

Sapp, Ellen ;

Osborn, Maire F. ;

Difiglia, Marian ;

Aronin, Neil ;

Khvorova, Anastasia .

MOLECULAR THERAPY-NUCLEIC ACIDS, 2015, 4 :e266

[3] Antisense Oligonucleotides Used to Target the DUX4 mRNA as Therapeutic Approaches in FaciosScapuloHumeral Muscular Dystrophy (FSHD) [J].

Ansseau, Eugenie ;

Vanderplanck, Celine ;

Wauters, Armelle ;

Harper, Scott Q. ;

Coppee, Frederique ;

Belayew, Alexandra .

GENES, 2017, 8 (03)

[4] Biodistribution of phosphodiester and phosphorothioate siRNA [J].

Braasch, DA ;

Paroo, Z ;

Constantinescu, A ;

Ren, G ;

Öz, OK ;

Mason, RP ;

Corey, DR .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2004, 14 (05) :1139-1143

[5] Novel Hydrophobically Modified Asymmetric RNAi Compounds (sd-rxRNA) Demonstrate Robust Efficacy in the Eye [J].

Byrne, Michael ;

Tzekov, Radouil ;

Wang, Yi ;

Rodgers, Amanda ;

Cardia, James ;

Ford, Glenna ;

Holton, Katherine ;

Pandarinathan, Lakshmipathi ;

Lapierre, Jennifer ;

Stanney, William ;

Bulock, Karen ;

Shaw, Sharon ;

Libertine, Lyn ;

Fettes, Kevin ;

Khvorova, Anastasia ;

Kaushal, Shalesh ;

Pavco, Pamela .

JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS, 2013, 29 (10) :855-864

[6] Lipophilic siRNAs mediate efficient gene silencing in oligodendrocytes with direct CNS delivery [J].

Chen, Qingmin ;

Butler, David ;

Querbes, William ;

Pandey, Rajendra K. ;

Ge, Pei ;

Maier, Martin A. ;

Zhang, Ligang ;

Rajeev, Kallanthottathil G. ;

Nechev, Lubomir ;

Kotelianski, Victor ;

Manoharan, Muthiah ;

Sah, Dinah W. Y. .

JOURNAL OF CONTROLLED RELEASE, 2010, 144 (02) :227-232

[7] Endothelial Cell-Specific FGD5 Involvement in Vascular Pruning Defines Neovessel Fate in Mice [J].

Cheng, Caroline ;

Haasdijk, Remco ;

Tempel, Dennie ;

van de Kamp, Esther H. M. ;

Herpers, Robert ;

Bos, Frank ;

Den Dekker, Wijnand K. ;

Blonden, Lau A. J. ;

de Jong, Renate ;

Burgisser, Petra E. ;

Chrifi, Ihsan ;

Biessen, Erik A. L. ;

Dimmeler, Stefanie ;

Schulte-Merker, Stefan ;

Duckers, Henricus J. .

CIRCULATION, 2012, 125 (25) :3142-+

[8] Gene silencing following siRNA delivery to skin via coated steel microneedles: In vitro and in vivo proof-of-concept [J].

Chong, Rosalind H. E. ;

Gonzalez-Gonzalez, Emilio ;

Lara, Maria F. ;

Speaker, Tycho J. ;

Contag, Christopher H. ;

Kaspar, Roger L. ;

Coulman, Sion A. ;

Hargest, Rachel ;

Birchall, James C. .

JOURNAL OF CONTROLLED RELEASE, 2013, 166 (03) :211-219

[9] Transdermal Delivery of siRNA through Microneedle Array [J].

Deng, Yan ;

Chen, Jiao ;

Zhao, Yi ;

Yan, Xiaohui ;

Zhang, Li ;

Choy, Kwongwai ;

Hu, Jun ;

Sant, Himanshu J. ;

Gale, Bruce K. ;

Tang, Tao .

SCIENTIFIC REPORTS, 2016, 6

[10] Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits [J].

DiFiglia, M. ;

Sena-Esteves, M. ;

Chase, K. ;

Sapp, E. ;

Pfister, E. ;

Sass, M. ;

Yoder, J. ;

Reeves, P. ;

Pandey, R. K. ;

Rajeev, K. G. ;

Manoharan, M. ;

Sah, D. W. Y. ;

Zamore, P. D. ;

Aronin, N. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (43) :17204-17209

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