IMIB - Institute for Molecular Infection Biology

Programming antisense oligonucleotides (ASOs)

The human body plays host to a large variety of microbes, which together form the microbiome. In recent decades, efforts to understand the microbiome have increased and many diseases have been associated with microbial composition. To measure effects of individual bacteria on health and disease, one needs to delete specific species. However, most currently available antibiotics result in non-specific killing of a broad range of bacteria.
An approach to target bacteria more specifically is the use of antisense oligonucleotides (ASOs). ASOs are small, single stranded oligonucleotides that can bind to specific genomic targets when their sequences are complementary (e.g. mRNAs of essential genes).
ASOs are coupled to small cell-penetrating peptides (CPP), carrying them into cells where ASOs bind to their target mRNA sequence and inhibit translation. If essential genes are targeted it can result in specific killing of bacteria. The fact that ASOs can be designed exactly to sequences of interest makes them exciting candidates for new, highly specific antibiotics.
My goal is to computationally investigate various parameters of ASO mechanisms, such as off-target effects, binding specificity, CPP toxicity, etc. To achieve this, I will use data from RNA-sequencing, ribosome profiling and metagenomics experiments and try to establish algorithms to predict effects of ASOs prior to application.