Posters

Oxford Symposia - 5th Annual

OLIGO 2019 OXFORD:

Antisense & Therapeutic Nucleic Acids

1-2 April 2019, St Edmund Hall, Oxford, UK

Twitter: @LPMHealthcare, #OligoOx19

Posters and guidelines

Guidelines for poster preparation

Please prepare your poster in A1 portrait format (59cm wide x 84cm long). Do not laminate your poster, or use heavy printing material. Further information about poster sizes can be found on the following link:

http://tinyurl.com/y7bf

Posters larger than A1, or those in landscape orientation, will only be displayed subject to the availability of space.

Maximum capacity 10 A1 potrait posters

Please ensure you have appropriate permissions for the publication of your abstract from the original copyright holders. Should you wish your abstract not to be published, please notify us in writing at the time of abstract submission.

>>Where can I print my poster in Oxford?

Posters will be displayed for the full duration of the symposium.

Accepted posters

(Presenters in Bold)

If your abstract has been accepted for presentation but it does not appear in the list below, please let us know as soon as possible by email on Oligomer@LPMHealthcare.com.


Nanoscale interactions of biomolecules with graphene nanomaterials: NMR, DLS and fluorescence analysis of binding and transport

Budoor Al Umairi1 , David Clarkeand Elena Bichenkova1

School of Health Sciences, Faculty of Biology, Medicine and Health,  University of Manchester, Oxford Road, Manchester, M13 9PL, UK

Artificial ribonucleases (aRNases) are attractive agents for irreversible cleavage of pathogenic RNA sequences implicated in many diseases.  Peptidyl-oligonucleotide based aRNases can inactivate disease-relevant RNAs in a sequence-specific manner, thus providing a discovery platform for the development of novel therapeutics. However, their safe and effective delivery across biological barriers remains to be the key challenge.  Graphene, whose unique morphological, electrical and chemical properties offer tremendous potential for applications in biomedicine, has been identified as a potential nano-carrier for trafficking of various biomolecules. The rich π-system and high surface area of graphene are attractive for non-covalent interactions with bio-macromolecules. However, realising the full potential of graphene here is hindered by poor understanding of the nature and detail of its nanoscale interactions with biological molecules, including nucleic acids and peptides. The structural and electronic nature of the interaction between nucleic acid and graphene are complicated and unclear in both aqueous and organic media. In this research, we aim to identify structural features of biomolecules key for avid interaction with graphene, as a design route for a superior loading platform for biological molecules (e.g. aRNases), which will benefit from targeted delivery across biological membrane barriers. This can be achieved by identifying the principal mechanisms and structural rules underlying inter-molecular interactions of various biomolecules with the graphene monolayer. Thereby, we will gain the insight to tailor molecules able to compete effectively with graphene-graphene interactions in order to adhere well to graphene surfaces for drug delivery.  We investigate here the interactions between graphene/graphene oxide sheets of different sizes and catalytic peptides, oligonucleotides and peptide-oligonucleotide conjugates, using NMR, DLS and fluorescence spectroscopy.Tritium Radiolabelled Antisense Oligonucleotides for ADME Studies.


Jon Bloom1, Jack Haffenden1, Darren Price1, Vernon Wilson1, Stephen Harris2, Claire Henson2, Kathryn Webbley2, Hillary Beason3, Gina McMullen3, Michael Migawa3, Dan. Norris3 and Noah Post7

1Pharmaron UK Ltd, The Old Glassworks, Nettlefold Road, Cardiff,  CF24 5JQ, UK

2Pharmaron UK Ltd, Pegasus Way, Crown Business Park, Rushden, NN10 6ER, UK

3Ionis Pharmaceuticals Inc, 2855 Gazelle Ct.  Carlsbad, CA 92010, USA

Radiolabelling is an essential part of drug development. Using a radiolabelled compound, the absorption, distribution, metabolism and excretion (ADME) may be quantitatively determined. Most often carbon-14 is the isotope of choice. Compounds labelled with carbon-14 are easy to handle and the label can be placed in a metabolically stable part of the molecule. Oligonucleotides present some problems however. Due to the high potency of many oligos, the specific activity and hence detectability of carbon-14 is too low. Tritium may be used instead but this isotope is more susceptible to exchange than carbon-14 and so the position of label in the nucleotide must be carefully chosen. In this poster, we show how an antisense oligonucleotide was labelled with 3H and used in a bio-distribution study.


Peptidyl-Oligonucleotide conjugates to target miRNAs associated with poor prognosis in Cancer

Thomas Heyman1, David Clarke1, Olga Patutina2, Marina Zenkova2, Harmesh Aojula1 and Elena V. Bichenkova1 

1School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, M13 9PT, UK

2Institute of Chemical Biology and Fundamental Medicine SB RAS, 8 Lavrentiev Avenue, 630090, Novosibirsk, Russia

Cancer is one of the largest causes of mortality in the western world. Despite large interdisciplinary effort and considerable funding to support the development of more successful and less toxic anti-cancer therapies, surgery remains the single most effective modality for the treatment of cancer. Conventionally, chemotherapies aim to target DNA and cause enough DNA damage to induce cell death, whereas targeted therapies aim to inhibit specific proteins associated with disease. The main issues associated with these modalities are poor selectivity and off target effects resulting in severe systemic toxicity. We are currently developing novel therapeutics which recognise and cleave highly oncogenic miRNAs (i.e. miR-17, miR-21 and miR-155) that are commonly overexpressed in almost every cancer type and have associations with poor prognosis. These Peptidyl-Oligonucleotide conjugates are comprised of a recognition oligonucleotide motif attached to a catalytic peptide with cleavage capabilities. As each miRNA are posttranscriptional regulators of multiple gene targets, these therapeutics have the potential to downregulate expression of multiple genes whilst only interacting with a single type of miRNA. These novel peptidyl-oligonucleotide conjugates are fully characterised with NMR and mass spectrometry, and their binding and cleavage efficacy are assessed using various assays. The best candidates will be selected for functional, in vitro and in vivo assays. The selectivity and tuneability of this new class of drug enables them to potentially be used in countless medical applications, simply by changing the oligonucleotide recognition sequence to another target. This new type of therapeutic interventions has the potential to revolutionise the way we treat cancer and will have a positive impact on the health outcomes for patients.