Abstract
Several strategies based on synthetic oligonucleotides (ON) have been proposed to control gene expression. As for most biomolecules, however, delivery has remained a major roadblock for in vivo applications. Conjugation of steric-block neutral DNA mimics, such as peptide nucleic acids (PNA) or phosphorodiamidate morpholino oligonucleotides (PMO), to cell-penetrating peptides (CPP) has recently been proposed as a new delivery strategy. It is particularly suitable for sequence-specific interference with pre-mRNA splicing, thus offering various applications in fundamental research and in therapeutics. The chemical synthesis of these CPP-ON conjugates will be described as well as easy-to-implement assays to monitor cellular uptake, endosome leakage, and efficiency of splicing redirection.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Cell Membrane Permeability
-
Cell-Penetrating Peptides / chemistry
-
Cell-Penetrating Peptides / metabolism*
-
Disulfides / chemistry
-
Drug Carriers / chemistry
-
Drug Carriers / metabolism
-
Endocytosis
-
Flow Cytometry
-
HeLa Cells
-
Humans
-
Liposomes / metabolism
-
Luciferases / genetics
-
Maleimides / chemistry
-
Oligodeoxyribonucleotides / chemistry
-
Oligodeoxyribonucleotides / genetics
-
Oligodeoxyribonucleotides / metabolism
-
Oligonucleotides / chemistry
-
Oligonucleotides / genetics*
-
Oligonucleotides / metabolism*
-
Peptide Nucleic Acids / chemistry
-
Peptide Nucleic Acids / genetics
-
Peptide Nucleic Acids / metabolism
-
RNA Splicing / genetics*
-
Saponins / metabolism
Substances
-
Cell-Penetrating Peptides
-
Disulfides
-
Drug Carriers
-
Liposomes
-
Maleimides
-
Oligodeoxyribonucleotides
-
Oligonucleotides
-
Peptide Nucleic Acids
-
Saponins
-
maleimide
-
Luciferases