Descripción del proyecto
Obtener la secuencia de polímeros correcta con un coste adecuado
Millones de moléculas están hechas de unidades repetidas de componentes individuales (monómeros). El ADN y el ARN son polímeros naturales considerables que utilizan nucleótidos repetidos como componentes. Fabricar cadenas cortas de ARN modificado químicamente (oligonucleótidos) ha demostrado ser muy prometedor para desarrollar nuevas terapias. Actualmente, se consigue mediante síntesis en fase sólida, en la cual el oligo en crecimiento se une a un sustrato insoluble y se le añaden monómeros de uno en uno. La síntesis en fase sólida es difícil de efectuar a gran escala y la pureza resultante es baja, lo que se traduce en un alto coste. Exactmer, empresa británica incipiente, ha desarrollado una tecnología patentada que permite sintetizar polímeros totalmente en la fase líquida para superar estos obstáculos. A través del proyecto NANOLIGO, financiado con fondos europeos, se podrá comercializar esta tecnología, que tiene potencial para agilizar significativamente el desarrollo de fármacos poliméricos complejos novedosos y abaratar los costes de fabricación.
Objetivo
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.
Ámbito científico
- 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
Programa(s)
Régimen de financiación
ERC-POC-LS - ERC Proof of Concept Lump Sum PilotInstitución de acogida
HG1 2PW HARROGATE
Reino Unido
Organización definida por ella misma como pequeña y mediana empresa (pyme) en el momento de la firma del acuerdo de subvención.