Gene Therapy

The coding regions of many genes are interrupted by intervening sequences called introns. Gene transcription generates pre-messenger RNAs (pre-mRNAs) from which the introns are removed by splicing. This splice process results in mature mRNAs which are composed of the coding regions of genes and flanking exonic untranslated regions (5´ and 3´ UTR).
In 5 to 20% of patients with retinal degeneration, the disease-associated mutation leads to aberrant splicing of the respective gene. This mis-splicing is frequently caused by splice site mutations or silent DNA sequence alterations in exons. So far, no therapy is known to efficiently treat this type of mutation.
We currently develop gene therapeutic strategies to treat retinal diseases that are caused by splice site mutations. Using artificial genes (minigenes), we were able to show that components of the splice process can be manipulated to correct mis-spliced transcripts. We now continue to optimize this strategy for therapeutic applications in patient-derived cell lines and mouse models with different mutations affecting normal splicing. Our findings will also have impact on other diseases and gene therapeutic approaches.


Romain Da Costa (PhD student)
John Neidhardt (PhD)

Franco Pagani (MD), International Center for Genetic Engineering and Biotechnology, Trieste, Italy
Akihiro Ikeda (PhD), Department of Medical Genetics, University of Wisconsin-Madison, USA
Marius Ader (PhD), Center for Regenerative Therapies, Dresden, Germany