Related Experiment Video

Updated: Aug 14, 2025

Detection of Nuclear Blebbing and DNA Leakage in Mammalian Cells by Immunofluorescence
06:23

Detection of Nuclear Blebbing and DNA Leakage in Mammalian Cells by Immunofluorescence

Published on: January 17, 2025

848

Nuclear envelope morphology change upon repetitive treatment with modified antisense oligonucleotides targeting

Asmaa Abdelrahman1,2, Mette-Marie Wendelboe Nielsen1,3, Mette Halkjær Stage1,4

  • 1Department of Green Technology, Faculty of Engineering, University of Southern Denmark, Odense, Denmark.

Biochemistry and Biophysics Reports
|January 12, 2023
PubMed

Insights

Modified antisense oligonucleotides (ONs) targeting translation and splicing reduced nuclear envelope abnormalities and progerin expression in progeria cells. This offers a potential therapeutic strategy for Hutchinson-Gilford progeria syndrome.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by premature aging.
  • Nuclear envelope abnormalities, including lobulations, are a hallmark of progeria.
  • Progerin, an aberrant protein, accumulates and contributes to cellular dysfunction in HGPS.

Purpose of the Study:

  • To investigate the therapeutic potential of modified antisense oligonucleotides (ONs) in progeroid fibroblasts.
  • To assess the impact of ONs on nuclear morphology and gene expression related to progeria.

Main Methods:

  • Progeroid fibroblasts were treated with two modified antisense oligonucleotides designed to inhibit translation and spliceosome binding.
  • Confocal microscopy was employed to visualize and quantify changes in nuclear envelope morphology.
  • Polymerase chain reaction (PCR) was used to analyze RNA levels of lamin A and progerin.

Main Results:

  • Treatment with modified ONs led to a significant reduction in nuclear envelope lobulations.
  • Progerin expression was notably decreased in progeria cells following ONs transfection.
  • Changes in nuclear morphology correlated with altered gene expression at both RNA and protein levels.

Conclusions:

  • Modified antisense oligonucleotides demonstrate efficacy in ameliorating key cellular defects in progeria.
  • These ONs represent a promising therapeutic avenue for addressing progerin accumulation and nuclear abnormalities in HGPS.
Keywords:
Confocal microscopyGene silencingGenetic mutationRare disease

More Related Videos

Evaluation of Exon Inclusion Induced by Splice Switching Antisense Oligonucleotides in SMA Patient Fibroblasts07:02

Evaluation of Exon Inclusion Induced by Splice Switching Antisense Oligonucleotides in SMA Patient Fibroblasts

Published on: May 11, 2018

13.6K
Databases to Efficiently Manage Medium Sized, Low Velocity, Multidimensional Data in Tissue Engineering09:43

Databases to Efficiently Manage Medium Sized, Low Velocity, Multidimensional Data in Tissue Engineering

Published on: November 22, 2019

6.3K

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...
2.4K
Nuclear Export of mRNA02:31

Nuclear Export of mRNA

Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.7K
Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
21.6K
Nuclear Protein Sorting01:34

Nuclear Protein Sorting

Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
4.7K