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16
CONTENTS
0-8493-1141-1/02/$0.00+$1.50
© 2002 by CRC Press LLC
Cell-Penetrating Peptides
as Vectors for Delivery
of Nucleic Acids
Andres Valkna, Ursel Soomets, and Ülo Langel
16.1 Introduction ..................................................................................................347
16.2 Transport of Naked Oligonucleotides..........................................................348
16.3 Delivery Strategies .......................................................................................349
16.4 Peptide Vectors for Oligonucleotide Delivery.............................................350
16.4.1 Penetratin..........................................................................................350
16.4.2 Tat.....................................................................................................351
16.4.3 Transportan.......................................................................................354
16.4.4 MTS–NLS ........................................................................................354
16.4.5 pVEC................................................................................................356
16.4.6 Other Peptide Vectors.......................................................................356
16.4.7 Polylysine and Loligomers ..............................................................357
16.5 Conclusions ..................................................................................................358
Abbreviations.........................................................................................................358
References..............................................................................................................360
16.1 INTRODUCTION
Gene expression underlies important biological processes, including development,
immune defense, and tumorigenesis. Many pathological processes are known to
result from mutations that alter the way that genes are switched on and off. A current
goal in molecular medicine is the development of new strategies to interfere with
gene expression in living cells in the hope that novel therapies for human disease
will result from these efforts.
During recent years, oligonucleotides (ONs) and their stable analogs have
received remarkable attention as a rational way to design sequence-specific ligands
of nucleic acids. Antisense and ribozyme strategies are based on the formation of
Watson–Crick bonds between ribozyme or oligodeoxynucleotide (ODN) and complementary
RNA sequence. 1 An ODN can be used as a “decoy” to trap DNA-binding
347