Related Experiment Video

Updated: May 31, 2026

Sequence-specific and Selective Recognition of Double-stranded RNAs over Single-stranded RNAs by Chemically Modified Peptide Nucleic Acids
09:04

Sequence-specific and Selective Recognition of Double-stranded RNAs over Single-stranded RNAs by Chemically Modified Peptide Nucleic Acids

Published on: September 21, 2017

Cell-penetrating peptides-based strategies for the delivery of splice redirecting antisense oligonucleotides

Samir El Andaloussi1, Fatouma Said Hassane, Prisca Boisguerin

  • 1Department of Neurochemistry, Stockholm University, Stockholm, Sweden. samir.elandaloussi@dpag.ox.ac.uk

Methods in Molecular Biology (Clifton, N.J.)
|July 13, 2011
PubMed

Insights

Cell-penetrating peptides (CPPs) deliver splice-redirecting oligonucleotides (ONs) for cancer therapy. This study details new CPPs and a method to assess ON nuclear delivery, overcoming bioavailability challenges for genetic medicine.

Area of Science:

  • Molecular biology
  • Drug delivery systems
  • Oligonucleotide therapeutics

Background:

  • Human malignancies have molecular targets for oligonucleotide (ON)-based therapies.
  • Antisense ONs offer potential for splicing regulation, as many genes alternative splice and defects cause disease.
  • Poor bioavailability of nucleic acid drugs hinders ON implementation.

Purpose of the Study:

  • To develop novel cell-penetrating peptides (CPPs) for delivering splice-redirecting steric-block ONs.
  • To establish a quantitative assay for assessing ON nuclear delivery.
  • To overcome bioavailability limitations of oligonucleotide therapeutics.

Main Methods:

  • Chemical conjugation and non-covalent complexation of CPPs with steric-block ONs.
  • Development of a splice redirecting assay for quantitative assessment of ON nuclear delivery.
  • Utilizing CPPs as non-viral vectors for non-permeant biomolecules.

Main Results:

  • Successful delivery of splice redirecting steric-block ONs using novel CPPs.
  • Demonstration of both chemical conjugation and non-covalent complexation strategies.
  • Establishment of a robust assay for quantitative evaluation of ON nuclear delivery.

Conclusions:

  • Novel CPPs enable effective delivery of splice-redirecting ONs, addressing bioavailability challenges.
  • The developed assay provides a reliable method for assessing ON nuclear delivery.
  • This approach holds promise for advancing oligonucleotide-based therapies for genetic diseases and malignancies.

More Related Videos

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells10:06

Engineering Artificial Factors to Specifically Manipulate Alternative Splicing in Human Cells

Published on: April 26, 2017

Related Concept Videos

Experimental RNAi02:15

Experimental RNAi

RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
siRNA - Small Interfering RNAs02:30

siRNA - Small Interfering RNAs

Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
Conservative Site-specific Recombination and Phase Variation02:53

Conservative Site-specific Recombination and Phase Variation

Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
RNA Interference01:23

RNA Interference

RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
Site-Targeted Drug Delivery Systems: Polymeric Carriers01:24

Site-Targeted Drug Delivery Systems: Polymeric Carriers

Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...