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Harwell Campus UK

Our Science

The Nucleic Acid Therapy Accelerator (NATA) is a new national research initiative with a mission to accelerate the development of nucleic acid therapeutics

Our Vision

Nucleic acid therapeutics have emerged as a major class of biopharmaceuticals. Their development and use is currently limited by the technology for their manufacture and the lack of robust techniques to target their delivery to specific peripheral tissues. NATA Hub will address these challenges head-on, with a panel of novel approaches, and world-leading expertise. Our scientific team will devise and advise on efficient nucleic acid modifications and formulation strategies aiming to reach previously untargeted tissues with efficient, non-toxic delivery and clear therapeutic effects.

Our Hub

Through strong and sustainable collaborations with the main actors in the field, the NATA Hub will combine know-how and state-of-the-art nucleic acid technologies from the academia, biotech and industry worlds.

We believe at NATA that this unique multidisciplinary environment is essential to accelerate the translational research of nucleic acid-based therapeutics and develop new innovative technologies related to the field.

NATA’s science and expertise will be provided through two departments: Chemistry and Biology. The centre is disease agnostic with an initial focus on short oligonucleotide therapeutics (antisense oligonucleotides ASOs and small interfering RNAs siRNAs).

NATA’s toolbox and techniques will help answering the main questions about translational development: Target ID, oligonucleotides design & synthesis, off-target/safety prediction, precision targeting, ligand conjugation, efficacy in vitro/in vivo, distribution/uptake, quantification, DMPK/stability.

Our main areas of interest sit around tissue specific targeting, endosomal escape, novel manufacture methodologies, and new advanced conjugate modalities.

Facilities

The Research Complex at Harwell 

NATA Hub will be located at Harwell, an internationally recognised campus for scientific and technological innovation.

This cross-discipline scientific environment provides to NATA major opportunities to interact with UK based and worldwide academia and industry gaining access to novel technologies.

Our Departments

Chemistry

The chemistry department of the NATA Hub is positioned as a hub for innovation, equipped with state-of-the-art technologies for the development of fundamental nucleic acid chemistry, manufacturing capabilities and the development of delivery methods to accelerate the development of novel RNA-based therapeutics. 

Why Engage with us:

  • We can consult on the design of sequences and chemical modification patterns of all three classes of oligonucleotides (siRNA, ASOs gapmer and blockers) targeting any new target
  • We can manufacture, purify and characterize natural or modified oligonucleotides, including  new chemical modifications for nucleosides/tides, new modalities, ligands and conjugation methods or fluorescently-labelled oligonucleotides, detection and quantification of oligonucleotides in biological samples
  • Leverage our expertise in detection and characterization of trace impurities after synthesis or identification of metabolites after incubation or systemic injection via high-resolution mass spectrometry

Biology

Currently, siRNA- and antisense-based therapeutics have been licenced for targets in the liver, kidney, skeletal muscle, eye and spinal cord whilst mRNA-based vaccines are in the front line in the fight against Covid-19. The biology department at NATA Hub will deploy the latest technologies to examine novel approaches for the delivery of nucleic acid therapeutics into key organs/cells. We will work with key stakeholders in academia and industry to catalyse collaborative research and to provide education and support to advance nucleic acid-based therapeutics. 

Why Engage with us

  • We can consult on the best approach for developing an oligonucleotide therapy against your target
  • We can work with you to identify biologically active oligonucleotides in vitro and in vivo using state-of-art technologies
  • We can examine novel oligonucleotide delivery approaches in vitro and in vivo
  • We can work with you to examine important pre-clinical issues using as DMPK and toxicology
  • Leverage our expertise and resources for examining other applications of oligonucleotides e.g. vaccines, aptamers, CRISPR etc...

Equipment

Chemistry

The Chemistry Laboratory occupies approximately 100-meter squares in the newly built extension of the Research Complex at Harwell. Our instrumentation enables the cost-effective synthesis of screening quantities to mid-scale custom oligonucleotide synthesis, the incorporation of novel chemistries and conjugates, purification, and quality control, and the manufacture of high-quality materials for in vitro and in vivo validation of novel oligonucleotides therapeutics.


New Modalities and ligands Synthesis: The chemistry laboratory is furnished with standard chemistry synthesis equipment and extensive automated purification facilities, including a Pure C-815 Flash Advanced automated flash chromatography system with UV and ELS detection for purification of small molecules, and an automated -semipreparative HPLC. This setting allows the development of new ligands, new conjugate methodologies and new chemical modifications applied to oligonucleotide therapeutics.

Characterization of small molecules: NMR analysis are performed using a Bruker Avance III 400MHz NMR spectrometer equipped with a Broadband multinuclear (BBFOPlus) probe at the RCaH. With a wide range of observable nuclei and a automatic sample changer with 60 position carousel, this instrument can perform analysis on small molecule. Mass analysis can be performed on an Acquity Premier UPLC with PDA, QDa and MassLynx software.

RNA Synthesis and deprotection: NATA Hub has a Mermade 192X for a high-throughput oligonucleotide synthesis from 20 nanomole to 5 micromole scales and a Mermade 12 for medium throughput synthesis on 20 nanomole to 200 micromole scales. The removal of protective groups from newly-synthesised oligonucleotides is possible by gas phase chemistry using wavePREP DNA system.

RNA Purification: The chemistry laboratory is equipped with two complementary HPLC systems (Acquity Premier UPLC with PDA, FLD, Waters Analytical Fraction Manager and MassLynx software), a Waters Autopurification System with PDA and Masslynx Software for small-scale and scale-up purification, and a ÄKTA pure chromatography system for desalting or purification through size exclusion chromatography.

Quality Control System: Oligonucleotide masses are checked using an Acquity Premier UPLC with PDA, QDa and MassLynx software. The identification of impurities and quality control of oligonucleotides for test release is performed on a Acquity Premier with Synapt XS, MassLynx software and Waters Connect / UNIFI for next generation oligo data processing. 

High-throughput liquid handling solution: a Multidrop Combi with SMART 2 and an Andrew+ liquid handling robot are available to insure reliable, error-free and fully-automated lab workflows for formulation and testing.

Biology

The Biology Laboratory occupies approximately 120-meter squares (room 1.52, 1.40 and 1.51) on the first floor of the Research Complex at Harwell on the Harwell Campus. It contains the latest equipment for the measurement of RNA/protein expression and phenotypic changes in human and animal tissues/cells, that will be employed to measure the delivery and activity of nucleic acid therapeutics.  


Cell and Animal Models: NATA Hub has state of-the-art cell cultures and animal facilities (MRC Mary Lyons Centre) that will permit the screening of antisense, siRNAs and other nucleic acid-based therapeutics in cell lines, primary cells and animal models.

RNA Expression Analysis: The ability to undertake transcriptional profiling will be crucial to assessing the delivery and biological action of nucleic acid therapeutics. To this end, NATA Hub is equipped with the latest Illumina sequencer (NextSeq 2000) and supporting equipment for automated RNA extraction (Qiagen Tissue Lyser and Thermofisher KingFisherFlex), RNA/DNA quality control (Agilent Tapestation 4200), RNA shearing (Bioruptor) and liquid handling facilities for RNA library preparation (Andrews Robotics). Changes in individual mRNAs can be assessed by qRT-PCR (BioRad CFX96 Touch) and Quantigene analysis (Thermofisher) whilst 3D changes can be resolved by in situ hybridisation (see microscopy).

Protein Expression Analysis: The action of the nucleic based therapeutic at the protein level can be assessed using automated Western blotting (Protein Simple Jess) and immunohistochemistry (see microscopy).

Single cell analysis: To examine the action of nucleic acid therapeutics at the single cell level, NATA Hub is equipped with the BD FACS melody single cell sorter, Chromium 10X single cell sequencer and molecular machine CellCut (MMI) laser microdissection  

Histology/Microscopy: NATA Hub is equipped with state-of-the-art equipment for the 3D detection of RNA and protein expression using an Olympus fluorescence microscope with MMI laser capture facilities and a BOND FX (for automated ISH and IHC).
 

Advisory Group  

 

 

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