Back to overview

Application of oligonucleotide mediated exon skipping in the treatment of Rheumatoid Arthritis

Scientists at Leiden University Medical Center have developed a method by which two mediators of the pathological response seen in inflammatory diseases such as RA can be modulated using anti-sense oligonucleotides and exon skipping.

The complement system is a part of the innate immune system which protects the host from micro-organisms such as bacteria and other foreign and abnormal cells. Inflammatory diseases such as rheumatoid arthritis (RA) have an excessive and inappropriate complement activation and excessive concentrations of interleukin-1
(IL-1) in the blood. Complement component 5 (C5) and IL-1 are important mediators of inflammation in RA.

Exon skipping is a term for the binding of antisense oligonucleotides (AONs) to their target exon on pre-mRNA, preventing recognition by the splicing machinery, resulting in non-functional or truncated functional proteins. Scientists at the LUMC have designed two types of AONs. One is able to specifically decrease the levels of C5a whilst the second is able to neutralizes the effects of IL-1 by increasing the levels of soluble IL-1 receptor accessory protein (sIL-1RAcP).  Successful skipping of target exons in C5a and IL-1AcP pre-mRNA has already been demonstrated both in vitro and in vivo. This AON-based therapy is believed to be more specific, safer and cheaper than other nucleotide-based therapies such as gene therapy.

Partner companies are now sought for research collaborations in this field, and licensing of key technologies available at the institutions. Specifically we are looking for companies with a franchise in the treatment of autoimmune disorders.

Key benefits

  • Specific targeting of C5a
  • Deletion of the trans-membrane encoding exon of IL-1AcP releases soluble IL-1AcP which then neutralizes IL-1
  • Successful skipping of exons has been demonstrated in vitro and in vivo
  • More specific, safer and cheaper than virus-based therapies.
  • World-leading expertise in exon skipping


Treatment of inflammatory diseases, such as Rheumatoid Arthritis

Development stage

Successful skipping of target exons in C5a and IL-1AcP pre-mRNA has been demonstrated in vitro and in vivo 

Luris reference number


Patent status

National phase

Data available on request

Non-confidential and confidential presentations

Further information

Wilbert van Workum Knowledge Broker Human Genetics +31-71-527 2508 Room number: 1.16