Descrizione del progetto
Ottenere la giusta sequenza polimerica al giusto costo
Milioni di molecole sono costituite da unità ripetitive di singoli elementi costitutivi (monomeri). Il DNA e l’RNA sono importanti polimeri naturali costituiti da nucleotidi ripetuti come elementi costitutivi. La produzione di brevi filamenti di RNA modificato chimicamente (oligonucleotidi) ha mostrato grandi promesse per lo sviluppo di nuove terapie. Attualmente è ottenuta utilizzando la sintesi in fase solida in cui l’oligo in crescita è legato a un substrato insolubile e i monomeri vengono aggiunti uno alla volta. La sintesi in fase solida è difficile da replicare e la purezza risultante è bassa, il che porta a prezzi elevati. Per superare questi ostacoli, la start-up britannica Exactmer ha sviluppato una tecnologia brevettata che consente la sintesi di polimeri interamente in fase liquida. Il progetto NANOLIGO, finanziato dall’UE, porterà questa tecnologia sul mercato nella speranza di accelerare considerevolmente lo sviluppo di nuovi farmaci polimerici complessi e ridurre i costi di produzione.
Obiettivo
Since the Nobel Prize winning discovery of small interfering RNA its specificity and selectivity have driven the pharmaceutical industry to design 15- to 25-mer oligonucleotide analogues as a new class of drugs. These offer exciting new therapeutic possibilities for example in rare diseases, but also large patient population indications including cardiovascular disease, and viral pandemics such as Covid-19. However, the high cost and limited scalability of manufacturing these complex polymeric molecules using solid phase synthesis is holding back benefits for thousands of patients – and has motivated us to seek an improved technology for oligo synthesis.
ERC Advanced Grant 786398 is funding research investigating a new technology platform for the fabrication of defined monomer sequence polymers - Nanostar Sieving. Our preliminary research into oligo synthesis using Nanostar Sieving has found that it is potentially both feasible and game-changing. NANOLIGO seeks proof-of-concept that Nanostar Sieving can unlock the tremendous potential of oligos through dramatically reducing production cost and increasing production capacity. We will work with RNA oligos – key targets for novel APIs – which are currently produced by solid phase synthesis, and show that these can be made entirely in the liquid phase, with unprecedentedly high purity, efficient chemistry and lower solvent consumption. Crucially, membrane separations are readily scaled up, making this process a strong candidate for kg-scale oligo production.
The PI and members of his research team have founded a start-up, Excatmer, to ensure the results of the ERC Grant have impact. We will carry out the PoC project at Exactmer, so that if we are successful the technology can be more rapidly developed and scaled up, leading to significant economic benefits. We are driven by a desire to make oligonucleotide therapies affordable and so available to patients as rapidly as possible.
Campo scientifico
- medical and health scienceshealth sciencespublic healthepidemiologypandemics
- natural scienceschemical sciencespolymer sciences
- medical and health scienceshealth sciencesinfectious diseasesRNA virusescoronaviruses
- medical and health sciencesclinical medicinecardiologycardiovascular diseases
- natural sciencesbiological sciencesgeneticsRNA
Programma(i)
Meccanismo di finanziamento
ERC-POC-LS - ERC Proof of Concept Lump Sum PilotIstituzione ospitante
HG1 2PW HARROGATE
Regno Unito
L’organizzazione si è definita una PMI (piccola e media impresa) al momento della firma dell’accordo di sovvenzione.