Cell penetrating PNA constructs regulate galanin receptor levels and modify pain transmission in vivo

@article{Pooga1998CellPP,
  title={Cell penetrating PNA constructs regulate galanin receptor levels and modify pain transmission in vivo},
  author={Margus Pooga and Ursel Soomets and Mattias H{\"a}llbrink and Andres Valkna and K{\"u}lliki Saar and Khadijeh Rezaei and Ulrika Kahl and Jingcan Hao and Xiao-jun Xu and Zsuzsanna Wiesenfeld‐Hallin and Tomas G. M. H{\"o}kfelt and Tam{\'a}s B{\'a}rtfai and {\"U}lo Langel},
  journal={Nature Biotechnology},
  year={1998},
  volume={16},
  pages={857-861}
}
Peptide nucleic acids (PNAs) form stable and tight complexes with complementary DNA and/or RNA and would be promising antisense reagents if their cellular delivery could be improved. We show that a 21-mer PNA, complementary to the human galanin receptor type 1 mRNA, coupled to the cellular transporter peptides, transportan or pAntennapedia(43–58), is efficiently taken up into Bowes cells where they block the expression of galanin receptors. In rat, the intrathecal administration of the peptide… 
Intrathecal administration of PNA targeting galanin receptor reduces galanin-mediated inhibitory effect in the rat spinal cord
TLDR
It is shown that intrathecal injection of an unmodified antisense PNA complementary to the rat galanin receptor type 1 (GalR1) mRNA is able to block the inhibitory effect of i.t. administered Galanin on spinal nociceptive transmission.
Targeting of antisense PNA oligomers to human galanin receptor type 1 mRNA
TLDR
Specific results of this study demonstrate 20-fold more efficient antisense down-regulation of GalR1 as achieved before, and are of high impact in designing antisense oligomers.
Antisense inhibition of delta-opioid receptor gene function in vivo by peptide nucleic acids.
TLDR
Results demonstrate that peptide nucleic acids are effective antisense agents in vivo and suggest that PNA may be a useful alternative to phosphodiester or phosphorothioate oligonucleotides, or variants thereof, for determination of gene function in vivo.
Cell-Penetrating Peptide-Mediated Delivery of Peptide Nucleic Acid (PNA) Oligomers.
TLDR
This protocol presents a synthesis strategy for covalently linking a cell-penetrating peptide (CPP) to PNA using a disulfide bridge, which can improve existing protocols for protein knockdown as well as DNA delivery, due to its relatively high efficacy and low toxicity.
Cell penetrating peptide conjugates of steric block oligonucleotides☆
TLDR
Two new families of arginine-rich CPPs named (R-Ahx-R)4 AhxB and R6Pen allow efficient nuclear delivery of splice correcting PNA and PMO at micromolar concentrations in the absence of endosomolytic agents.
RNA targeting with peptide conjugates of oligonucleotides, siRNA and PNA.
TLDR
The most promising results to date have been with a 16-mer PNA conjugated to the CPP Transportan or a double CPP R(6)-Penetratin, where Tat-dependent trans-activation inhibition in HeLa cells is demonstrated.
Cellular uptake of antisense oligonucleotides after complexing or conjugation with cell-penetrating model peptides.
TLDR
The results question the common belief that the increased biological activity of oligonucleotides after derivatization with membrane permeable peptides may be primarily due to improved membrane translocation.
Peptide-mediated cellular delivery of antisense oligonucleotides and their analogues
  • M. Gait
  • Biology, Medicine
    Cellular and Molecular Life Sciences CMLS
  • 2003
TLDR
This review contains a critical evaluation of claims for certain peptide-oligonucleotide conjugates to translocate into cultured cells by a non-energy-dependent nonendosomal route.
Cooperative Cellular Uptake and Activity of Octaarginine Antisense Peptide Nucleic Acid (PNA) Conjugates
TLDR
The results are compatible with an endosomal uptake mechanism in which the endocytosis event is induced by multiple CPP–PNA binding to the cell surface requiring a certain CPP density, possibly in terms of nanoparticle number and/or size, to be triggered.
Conjugates of Antisense Oligonucleotides with the Tat and Antennapedia Cell-Penetrating Peptides: Effects on Cellular Uptake, Binding to Target Sequences, and Biologic Actions
TLDR
This assay clearly demonstrates the delivery of functional antisense molecules to the splicing machinery within the nucleus andjugation with cell-penetrating peptides enhances oligonucleotide delivery to the nucleus without interfering with the base-pairing function of antisense oligon nucleotides.
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