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Technology
Our proprietary protein aggregation technology: addressing unsolved challenges in drug discovery
A novel mechanism of action
Aelin Therapeutics has created an entirely new therapeutic modality with its proprietary Pept-in technology platform. Pept-ins are molecules capable of selectively driving the aggregation of specific target proteins, resulting in protein knock-down and/or proteostatic collapse of pathological cells. This enables functional inhibition of key proteins, blocking disease processes or resulting in cell death, granting Pept-ins a broad therapeutic potential.
Using aggregation prone regions as barcodes to target proteins
Aggregation of proteins in nature is driven by short amino acid stretches, called aggregation prone regions (APRs), within the protein sequence. Most proteins possess at least one APR, and most APRs are unique within the proteome. Pept-ins are designed based on the APR barcode to drive the aggregation of specific target proteins, resulting in protein knock-down and/or proteostatic collapse of pathological cells.
Unlocking the potential
The potential of the technology extends to all mammalian, bacterial and viral proteins. Aelin’s versatile in silico technology applies structural bioinformatics and machine learning to design sequence-specific, cell-permeable Pept-ins for an as yet unlimited range of disease indications.
ATHENA: Our proprietary in silico compound design engine
Our unique ATHENA in silico design engine follows a sequence specific structural bioinformatics and machine learning approach fueling fast selection of potential candidates. Our approach enables faster and easier prediction of active compounds than other approaches and includes the use of protein folding and misfolding models for further accuracy with a high success rate and short timeframe from design to hit.
APRs unique to a certain protein can be chosen, leading to the very selective knock-down of that specific, single protein. In contrast, APRs that match highly similar sequences shared by all proteins in a family can also be selected. Each of these approaches drives a distinct biological reaction and can be used to control the therapeutic effect. For example, the loss of function of a vital protein is demonstrated by the growth inhibition of tumor cells when targeting the oncogenic protein, whereas the process of inducing broad protein aggregation can lead to pathogen cell death, as observed in bacteria.
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Pept-ins can reach an undruggable and intracellular target space
Pept-ins are addressing the unsolved challenge of reaching undruggable proteins. Their design, consisting of APRs, flanked by charged residues and coupled by a short linker, allow them to remain stable in solution and permeate cells.
Pept-in discovery
2022
Input proteome
Physiological insights of the disease indication inform selection of the target
2022
Computational analysis
We identify and analyze the APR sequences of the target protein
2022
APR identification
Our algorithm determines the most promising APR sequences are chosen for Pept-in design
2022
Pept-in design
From the chosen APRs, we generate a library of Pept-ins
2022
Functional testing
In vitro screening of the library enables identification of functionally active Pept-ins, which we subsequently characterize, optimize and test in vivo
