Module 4 - Methylation Profiling and Gene Therapy Tolerance

Recent studies have clearly demonstrated that therapeutic viral vectors can have a strong and long lasting epigenetic effect on target cells - either in the CpG islands around the vector promoter region which leads to transgene expression silencing, or globally in the target cells. These effects have not been characterized in depth yet. We monitor the global methylation changes and perform a high resolution quantitative assessment of CpG methylation level of relevant genomic regions. Those epigenetic alternations caused by viral vector infection are analyzed integrating whole transcriptome data and viral vector IS-data. This approach helps us to address the side effects of gene therapy such as target cell expression alternation, aberrant transcripts and vector read-through transcripts as well as vector silencing in a detailed and high-throughput manner.