Novel non-endocytic delivery of antisense oligonucleotides

Citation
S. Dokka et Y. Rojanasakul, Novel non-endocytic delivery of antisense oligonucleotides, ADV DRUG DE, 44(1), 2000, pp. 35-49
Citations number
101
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Pharmacology & Toxicology
Journal title
ADVANCED DRUG DELIVERY REVIEWS
ISSN journal
0169-409X → ACNP
Volume
44
Issue
1
Year of publication
2000
Pages
35 - 49
Database
ISI
SICI code
0169-409X(20001031)44:1<35:NNDOAO>2.0.ZU;2-J
Abstract
Antisense oligonucleotides (ONs) have several properties that make them att ractive as therapeutic agents. Hybridization of antisense ONs to their comp lementary nucleic acid sequences by Watson-Crick base pairing is a highly s elective and efficient process. Design of therapeutic antisense agents can be made more rationally as compared to most traditional drugs, i.e., they c an be designed on the basis of target RNA sequences and their secondary str uctures. Despite these advantages, the design and use of antisense ONs as t herapeutic agents are still faced with several obstacles. One major obstacl e is their inefficient cellular uptake and poor accessibility to target sit es. In this article, we will discuss key barriers affecting ON delivery and approaches to overcome these barriers. Current methods of ON delivery will be reviewed with an emphasis on novel non-endocytic methods of delivery. O Ns are taken up by cells via an endocytic process. The process of ON releas e from endosomes is a very inefficient process and, hence, ONs end up being degraded in the endosomes. Thus, ONs do not reach their intended site of a ction in the cytoplasm or nucleus. Delivery systems ensuring a cytoplasmic delivery of ONs have the potential to increase the amount of ON reaching th e target. Here, we shall examine various ON delivery methods that bypass th e endosomal pathway. The advantages and disadvantages of these methods comp ared to other existing methods of ON delivery will be discussed. (C) 2000 E lsevier Science B.V. All rights reserved.