Platform for the selection and validation of diagnostic and therapeutic antiPTM antibodies

Challenge

No FDA-approved drug targets a PTM protein because no technology allows to directly validate these targets. There is a great need for methods that allow to functionally distinguish proteins that differ from each other only for post-translational modifications and to selectively interfere with the post-translationally modified subset of a given protein. Cellular interference studies are necessary to functionally validate a target, to initiate drug development against a given target or to understand the role of a gene in the genesis of a disease.

Technology

The solution is based on the PISA technology (PISA stands for Post-translational Intracellular Silencing Antibodies). Using yeast cells we select from recombinant antibody libraries those antibodies that specifically recognize only a particular protein variant with a specific PTM. With this antibody we can selectively interfere with just that specific protein variant. In the selection we use yeast cells that express the modified protein in its native form, i.e. exactly as it is present in the cells, unlike other methods which instead use only a fragment of the protein with the modification. Furthermore, we know the genetic code (DNA) of our antibodies and therefore they can be used as genes (gene therapy) or in protein form (immunotherapy). We can also equip antibodies with components that allow them to acquire additional functions such as eliminating the protein to which they bind or make them usable for imaging as “sensor”.

Commercial Opportunity

 Equipment used in laboratories and genomic tools are costy. This could represent a first opportunity for the AntiBody Platform as a Service business model that could be provide also by public research laboratories.

Development Status

TRL is actually 4 and is expected to increase from 4 to 6, since the Project has been admitted for a Proof-of-Concept (POC) funding by the Italian Ministry for Economic Development. The aspiration of this POC initiative is to develop, by mid 2022, a Minimal Viable product that would gain attention of potential investors and industrial partners. The research group is also considering the creation of a spin-off at Scuola Normale Superiore aiming to bridge the gap between the industry and academia.

Patent Situation

The following patents are being granted: CA3003555; EP3371596 and US2019361013.

Further Reading

Alonso, A.D. et al. J Biol Chem 285, 30851-60 (2010).

Chirichella, M. et al, Nat. Methods 14, 279 (2017).

Iqbal, K. et al.Front Neurol 4, 112 (2013).

Jin, N. et al. J Biol Chem 290, 15219-37 (2015).

Liu, F. et al. Panminerva Med 48, 97-108 (2006).

Wang, X. et al. J Alzheimers Dis 45, 423-35 (2015).

Karve, T.M. & Cheema, A.K. J Amino Acids 2011, 207691 (2011).

Xu H., Wang Y., Lin S., Deng W., Di Peng, Cui Q., Xue Y. Genomics Proteomics Bioinformatics, 16:244-251 (2018).