Chemical modifications of nucleic acid drugs and their delivery systems for gene-based therapy

被引：138
作者：
Chen, Changmai [1 ]
Yang, Zhenjun [1 ]
Tang, Xinjing [1 ]
机构：
[1] Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
来源：
MEDICINAL RESEARCH REVIEWS | 2018年 / 38卷 / 03期
基金：
中国国家自然科学基金;
关键词：
antisense oligonucleotides; chemical modifications; gene-based therapeutics; gene delivery; nucleic acid drugs; precision medicine; siRNA; IN-VIVO DELIVERY; SMALL INTERFERING RNA; TRIGGERED CHARGE-REVERSAL; VON-WILLEBRAND-FACTOR; ANTISENSE OLIGONUCLEOTIDE; SIRNA DELIVERY; TARGETED DELIVERY; OPEN-LABEL; CELLULAR UPTAKE; MESSENGER-RNA;
D O I：
10.1002/med.21479
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Gene-based therapy is one of essential therapeutic strategies for precision medicine through targeting specific genes in specific cells of target tissues. However, there still exist many problems that need to be solved, such as safety, stability, selectivity, delivery, as well as immunity. Currently, the key challenges of gene-based therapy for clinical potential applications are the safe and effective nucleic acid drugs as well as their safe and efficient gene delivery systems. In this review, we first focus on current nucleic acid drugs and their formulation in clinical trials and on the market, including antisense oligonucleotide, siRNA, aptamer, and plasmid nucleic acid drugs. Subsequently, we summarize different chemical modifications of nucleic acid drugs as well as their delivery systems for gene-based therapeutics in vivo based on nucleic acid chemistry and nanotechnology methods.
引用
收藏
页码：829 / 869
页数：41
相关论文
共 183 条
[1]   Living the PCSK9 Adventure: from the Identification of a New Gene in Familial Hypercholesterolemia Towards a Potential New Class of Anticholesterol Drugs [J].
Abifadel, Marianne ;
Elbitar, Sandy ;
El Khoury, Petra ;
Ghaleb, Youmna ;
Chemaly, Melody ;
Moussalli, Marie-Line ;
Rabes, Jean-Pierre ;
Varret, Mathilde ;
Boileau, Catherine .
CURRENT ATHEROSCLEROSIS REPORTS, 2014, 16 (09)
[2]   Phenotypic heterogeneity of the endothelium I. Structure, function, and mechanisms [J].
Aird, William C. .
CIRCULATION RESEARCH, 2007, 100 (02) :158-173
[3]   Attacking the genome: emerging siRNA nanocarriers from concept to clinic [J].
Alabi, Christopher ;
Vegas, Arturo ;
Anderson, Daniel .
CURRENT OPINION IN PHARMACOLOGY, 2012, 12 (04) :427-433
[4]   Intracellular delivery of an anionic antisense oligonucleotide via receptor-mediated endocytosis [J].
Alam, Md Rowshon ;
Dixit, Vidula ;
Kang, Hyunmin ;
Li, Zi-Bo ;
Chen, Xiaoyuan ;
Trejo, Joann ;
Fisher, Michael ;
Juliano, Rudy L. .
NUCLEIC ACIDS RESEARCH, 2008, 36 (08) :2764-2776
[5]   Multivalent Cyclic RGD Conjugates for Targeted Delivery of Small Interfering RNA [J].
Alam, Md Rowshon ;
Ming, Xin ;
Fisher, Michael ;
Lackey, Jeremy G. ;
Rajeev, Kallanthottathil G. ;
Manoharan, Muthiah ;
Juliano, Rudy L. .
BIOCONJUGATE CHEMISTRY, 2011, 22 (08) :1673-1681
[6]   Atu027, a Liposomal Small Interfering RNA Formulation Targeting Protein Kinase N3, Inhibits Cancer Progression [J].
Aleku, Manuela ;
Schulz, Petra ;
Keil, Oliver ;
Santel, Ansgar ;
Schaeper, Ute ;
Dieckhoff, Britta ;
Janke, Oliver ;
Endruschat, Jens ;
Durieux, Birgit ;
Roeder, Nadine ;
Loeffler, Kathrin ;
Lange, Christian ;
Fechtner, Melanie ;
Moepert, Kristin ;
Fisch, Gerald ;
Dames, Sibylle ;
Arnold, Wolfgang ;
Jochims, Karin ;
Giese, Klaus ;
Wiedenmann, Bertram ;
Scholz, Arne ;
Kaufmann, Joerg .
CANCER RESEARCH, 2008, 68 (23) :9788-9798
[7]   A phase II trial of intraperitoneal EGEN-001, an IL-12 plasmid formulated with PEG-PEI-cholesterol lipopolymer in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer: A Gynecologic Oncology Group study [J].
Alvarez, Ronald D. ;
Sill, Michael W. ;
Davidson, Susan A. ;
Muller, Carolyn Y. ;
Bender, David P. ;
DeBernardo, Robert L. ;
Behbakht, Kian ;
Huh, Warner K. .
GYNECOLOGIC ONCOLOGY, 2014, 133 (03) :433-438
[8]   Diversifying microRNA sequence and function [J].
Ameres, Stefan L. ;
Zamore, Phillip D. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2013, 14 (08) :475-488
[9]   Targeting von Willebrand factor as a novel anti-platelet therapy; Application of ARC1779, an Anti-vWF aptamer, against thrombotic risk [J].
Bae, Ok-Nam .
ARCHIVES OF PHARMACAL RESEARCH, 2012, 35 (10) :1693-1699
[10]   Immunoprotein-Mediated siRNA Delivery [J].
Balmer, Nicole ;
Berdel, Wolfgang E. ;
Baeumer, Sebastian .
MOLECULAR PHARMACEUTICS, 2017, 14 (05) :1339-1351
12345678910