Toft Sørensen Lab

My group invents, and applies, novel viral genetic tools that enable the uncovering of neuronal plasticity mechanisms and animal behavior that otherwise would be impossible to achieve with existing technologies. This also includes exploring how viral gene therapy can be used for potential clinical application to address unmet needs in patients with CNS disorders. Through rational approaches, we engineer DNA that encodes for unconventional recombinant peptides, which upon translation assembly themselves into multimeric peptides or become twisted. By such, the virally expressed peptides can acquire superior and desired properties in terms of higher affinity and target specificity, and capable of interacting with synaptic-associated proteins not normally regarded as traditional drug targets. Because we further harness on the versatile nature of viral vectors that allows for high spatial and/or temporal precision, these genetic tools serve as extremely powerful measures for studying and manipulating brain functions as well as representing clinical relevant solutions for various neurological conditions.   

Pathological pain conditions

The lab has a particular interest in understanding pain circuits and treating pathology pain conditions. For this, we apply our viral-genetic technology platforms in various pain models using both wild-type and transgenic mice.

Example of two gene therapy approaches employed in the lab. AAVs packaged with PHP.eB and PHP.s capsids and administrated by a single intravenous injection are selectively infecting CNS and PNS (i.e. dorsal root ganglion), respectively. Both AAVs drive the expression of a dimeric peptide, engineered in the lab, that targets the scaffolding protein PICK1 in neurons. Besides the dimeric peptide, the AAV vectors express Cre-recombinase and EGFP that allow for visualization of infected neurons in red (tdTomato) and green (EGFP) color. Both gene therapy approaches provide complete and sustained pain relief in models of neuropathic pain.     

Alzheimer's disease

In this disclosed project having different tracks, we aim to reduce and even reverse maladaptive plasticity and morphological changes occurring at the synaptic level in mouse models of Alzheimer’s disease.