Related Experiment Video

Updated: Jun 18, 2026

Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
14:20

Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?

Published on: June 13, 2014

PNA-mediated modulation and redirection of Her-2 pre-mRNA splicing: specific skipping of erbB-2 exon 19 coding for

Stanislava Pankratova1, Birgit N Nielsen, Takehiko Shiraishi

  • 1Department of Cellular and Molecular Medicine, The Panum Institute, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen N, Denmark.

International Journal of Oncology
|December 4, 2009
PubMed

Insights

Researchers developed peptide nucleic acid (PNA) oligomers to interfere with erbB-2 gene splicing. These compounds effectively induced exon 19 skipping in cancer cells, offering a potential new strategy for cancer drug discovery.

Area of Science:

  • Molecular Biology
  • Cancer Therapeutics
  • Antisense Technology

Background:

  • The Her-2 receptor, encoded by the erbB-2 gene, is a key target in specific breast cancer subtypes and is implicated in various other cancers.
  • Antisense-mediated splicing interference offers a potential therapeutic strategy to modulate erbB-2 expression.

Purpose of the Study:

  • To investigate the efficacy of peptide nucleic acid (PNA) oligomers in manipulating erbB-2 pre-mRNA splicing.
  • To identify PNA oligomers that specifically induce skipping of exon 19 of the erbB-2 gene.

Main Methods:

  • Design and synthesis of PNA oligomers targeting specific intron-exon junctions of the erbB-2 pre-mRNA.
  • Assessment of PNA oligomer activity on mRNA splicing in cultured SK-BR-3 and HeLa cancer cells.

Main Results:

  • Identified specific PNA oligomers that effectively induce skipping of exon 19 in erbB-2 pre-mRNA.
  • Demonstrated the activity of these PNA oligomers in relevant cancer cell lines (SK-BR-3 and HeLa).

Conclusions:

  • The identified PNA oligomers show promise for therapeutic applications by inducing dominant-negative, non-functional Her-2 protein variants.
  • Antisense-mediated exon skipping represents a viable drug discovery approach for targeting erbB-2 in cancer treatment.

Related Concept Videos

Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
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...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...