Aelin Therapeutics pioneers its proprietary Pept-inTM technology platform, a new paradigm in drug development. Pept-insTM are peptides capable of selectively driving the aggregation of specific proteins. This enables a targeted functional inhibition of key proteins, blocking disease processes or resulting in cell death, granting Pept-insTM a broad therapeutic potential.
Novel mechanism of action
Harnessing the power of
Proteins fold into a three-dimensional structure during and after synthesis. Some triggers, such as unfavorable environmental conditions or disruptions in the protein sequence caused by mutations, can disturb the folding process, result in aggregation of proteins, making them inactive.
Short sequences that promote this aggregation process, called aggregation prone regions (APR), have been identified inside almost all proteins, even those without a natural tendency to aggregate.
The Pept-inTM technology is based on the observation that this process can be specifically induced in almost any protein by seeding with a synthetic peptide containing the correct APR sequence, corresponding to the APR present in the target protein.
This means that almost any protein can be functionally knocked-out using Pept-insTM, independent of structural or functional protein class, without the need for an active site or an epitope on which small molecule drugs or biologicals rely.
AN UNEXPLORED TARGET SPACE
Pept-insTM consist of APRs, flanked by charged residues and coupled by a short linker. The charged residues stabilize the peptides and keep them in solution. They also promote cellular uptake. This opens up a completely novel target space. For example, transcription factors or intracellular scaffold proteins, which are difficult to target with classical antibody or small molecule approaches, are now within reach.
Engineering the therapeutic effect
In the APR identification phase, the specificity of the Pept-insTM can be engineered. APRs can be chosen that are unique to a specific protein, leading to a very selective knock-down of a single protein. In contrast, APRs can be selected that match highly similar sequences shared by all proteins in a family or among different bacterial strains.
This choice will drive a distinct physiological reaction and can be used to control the therapeutic effect. For example: