Immunoprotein-Mediated siRNA Delivery

被引:18
作者
Balmer, Nicole [1 ]
Berdel, Wolfgang E. [1 ]
Baeumer, Sebastian [1 ]
机构
[1] Univ Hosp Muenster, Dept Med A, Hematol & Oncol, Albert Schweitzer Campus 1, DE-48149 Munster, Germany
关键词
siRNA; biaccnjugate therapeutics; stabilization; specificity; therapeutic antibodies; RESPIRATORY SYNCYTIAL VIRUS; CELL-ENGAGING ANTIBODY; ACUTE MYELOID-LEUKEMIA; IN-VIVO; RNA INTERFERENCE; GENE DELIVERY; MONOCLONAL-ANTIBODIES; TARGETED THERAPY; TISSUE FACTOR; PEGYLATED IMMUNOLIPOSOMES;
D O I
10.1021/acs.molpharmaceut.6b01039
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
RNA interference strategies offer an alternative to small molecular drug targeting. Small interfering RNA (siRNA) constitutes a class of molecules that allows the effective and specific inhibition of the biosynthesis of any protein. Indeed, siRNA have emerged as a major tool in molecular biology techniques and an important approach to identify suitable therapy targets in cancer. However, siRNA therapy approaches in vivo are scarce. Two major problems hinder siRNA as a therapeutic tool: (1) delivery through the bloodstream leads to degradation or rapid renal clearance (stabilization) and (2) specific uptake by the desired cell type (specificity). This review summarizes the ongoing attempts to use RNAi against disease-causing factors. We compare methods to stabilize siRNA in different conjugates and that decorate these complexes with targeting molecules such as antibodies, single-chain Fv or Fab fragments, to enable specific uptake of the carriers by the respective cells. We propose the development of antibody-coupled siRNA complexes, which have shown to allow stabilization as well as targeted uptake of siRNA to cancer cells.
引用
收藏
页码:1339 / 1351
页数:13
相关论文
共 108 条
[1]   Ligand-targeted therapeutics in anticancer therapy [J].
Allen, TM .
NATURE REVIEWS CANCER, 2002, 2 (10) :750-763
[2]   Ku protein targeting by Ku70 small interfering RNA enhances human cancer cell response to topoisomerase II inhibitor and γ radiation [J].
Ayene, IS ;
Ford, LP ;
Koch, CJ .
MOLECULAR CANCER THERAPEUTICS, 2005, 4 (04) :529-536
[3]   Antibody-coupled siRNA as an efficient method for in vivo mRNA knockdown [J].
Baeumer, Nicole ;
Appel, Neele ;
Terheyden, Lisa ;
Buchholz, Frank ;
Rossig, Claudia ;
Mueller-Tidow, Carsten ;
Berdel, Wolfgang E. ;
Baeumer, Sebastian .
NATURE PROTOCOLS, 2016, 11 (01) :22-36
[4]   Antibody-Mediated Delivery of Anti-KRAS-siRNA In Vivo Overcomes Therapy Resistance in Colon Cancer [J].
Baeumer, Sebastian ;
Baeumer, Nicole ;
Appel, Neele ;
Terheyden, Lisa ;
Fremerey, Julia ;
Schelhaas, Sonja ;
Wardelmann, Eva ;
Buchholz, Frank ;
Berdel, Wolfgang E. ;
Mueller-Tidow, Carsten .
CLINICAL CANCER RESEARCH, 2015, 21 (06) :1383-1394
[5]   Tumor regression in cancer patients by very low doses of a T cell-engaging antibody [J].
Bargou, Ralf ;
Leo, Eugen ;
Zugmaier, Gerhard ;
Klinger, Matthias ;
Goebeler, Mariele ;
Knop, Stefan ;
Noppeney, Richard ;
Viardot, Andreas ;
Hess, Georg ;
Schuler, Martin ;
Einsele, Hermann ;
Brandl, Christian ;
Wolf, Andreas ;
Kirchinger, Petra ;
Klappers, Petra ;
Schmidt, Margit ;
Riethmueller, Gert ;
Reinhardt, Carsten ;
Baeuerle, Patrick A. ;
Kufer, Peter .
SCIENCE, 2008, 321 (5891) :974-977
[6]   Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging [J].
Bartlett, Derek W. ;
Su, Helen ;
Hildebrandt, Isabel J. ;
Weber, Wolfgang A. ;
Davis, Mark E. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (39) :15549-15554
[7]   Site-specific chemical modification of antibody fragments using traceless cleavable linkers [J].
Bernardes, Goncalo J. L. ;
Steiner, Martina ;
Hartmann, Isabelle ;
Neri, Dario ;
Casi, Giulio .
NATURE PROTOCOLS, 2013, 8 (11) :2079-2089
[8]   Infarction of tumor vessels by NGR-peptide-directed targeting of tissue factor: experimental results and first-in-man experience [J].
Bieker, Ralf ;
Kessler, Torsten ;
Schwoeppe, Christian ;
Padro, Teresa ;
Persigehl, Thorsten ;
Bremer, Christoph ;
Dreischalueck, Johannes ;
Kolkmeyer, Astrid ;
Heindel, Walter ;
Mesters, Rolf M. ;
Berdel, Wolfgang E. .
BLOOD, 2009, 113 (20) :5019-5027
[9]   RNA Interference (RNAi)-Based Therapeutics: Delivering on the Promise? [J].
Bobbin, Maggie L. ;
Rossi, John J. .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 56, 2016, 56 :103-122
[10]   Potential efficacy of cell-penetrating peptides for nucleic acid and drug delivery in cancer [J].
Bolhassani, Azam .
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER, 2011, 1816 (02) :232-246