Related Experiment Video

Updated: Feb 5, 2026

Evaluation of Exon Inclusion Induced by Splice Switching Antisense Oligonucleotides in SMA Patient Fibroblasts
07:02

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

Published on: May 11, 2018

14.4K

Antisense-Mediated Splice Modulation to Reframe Transcripts

Matthias Titeux1,2,3, Sandrina Turczynski1,2,3, Nathalie Pironon1,2,3

  • 1INSERM UMR 1163, Paris, France.

Methods in Molecular Biology (Clifton, N.J.)
|September 2, 2018
PubMed

Insights

Antisense-based splicing modulation can correct genetic disorders by restoring gene reading frames. This study demonstrates its efficacy in treating recessive dystrophic epidermolysis bullosa by targeting COL7A1 gene mutations.

Area of Science:

  • Genetics
  • Molecular Biology
  • Biochemistry

Background:

  • Genetic disorders often result from loss-of-function mutations (nonsense, frameshift) disrupting gene open reading frames.
  • These mutations lead to absent functional proteins via mRNA degradation (nonsense-mediated mRNA decay) or truncated protein degradation.

Purpose of the Study:

  • To develop and demonstrate the feasibility of antisense-based splicing modulation for treating genetic disorders.
  • To restore the open reading frame (ORF) and enable functional protein synthesis.

Main Methods:

  • Developed antisense-mediated exon skipping strategy.
  • Applied the approach to the COL7A1 gene, encoding type VII collagen, for recessive dystrophic epidermolysis bullosa.
  • Utilized the gene's structure (118 exons, 83 in-frame) for selective exon removal.

Main Results:

  • Demonstrated the feasibility and efficacy of antisense-mediated exon skipping.
  • Showcased the strategy's potential to reframe transcripts by selectively removing mutated exons.
  • Successfully applied the method to the COL7A1 gene as a model.

Conclusions:

  • Antisense-based splicing modulation is a viable therapeutic strategy for genetic disorders caused by ORF disruptions.
  • Exon skipping offers a promising approach to restore protein function in diseases like recessive dystrophic epidermolysis bullosa.
  • The COL7A1 gene's structure makes it particularly amenable to this exon skipping strategy.
Keywords:
AONCOL7A1Exon skippingOligoribonucleotidesRecessive dystrophic epidermolysis bullosaSplice modulation

More Related Videos

High Throughput In Vitro Assessment of Latency Reversing Agents on HIV Transcription and Splicing07:18

High Throughput In Vitro Assessment of Latency Reversing Agents on HIV Transcription and Splicing

Published on: January 22, 2019

6.2K
Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts11:19

Merging Absolute and Relative Quantitative PCR Data to Quantify STAT3 Splice Variant Transcripts

Published on: October 9, 2016

15.5K

Related Concept Videos

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...
25.2K
Alternative RNA Splicing02:18

Alternative RNA Splicing

5.2K
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...
60.7K
Transcription Factors02:16

Transcription Factors

Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
82.8K
Eukaryotic Transcription Activators02:42

Eukaryotic Transcription Activators

Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
12.8K
Transcription01:10

Transcription

Overview
Transcription is the process of synthesizing RNA from a DNA sequence by RNA polymerase. It is the first step in producing a protein from a gene sequence. Additionally, many other proteins and regulatory sequences are involved in the proper synthesis of messenger RNA (mRNA). Regulation of transcription is responsible for the differentiation of all the different types of cells and often for the proper cellular response to environmental signals.
Transcription Can Produce Different Kinds...
156.7K