Posters and Guidelines
Thank you for considering to present your work as a poster at Oligo 2024 Oxford. Please submit your poster abstract online within the advertised deadlines.
Poster preparation
- Page size: Prepare your poster as you would normally do for printing. You can prepare your poster in sizes A1 or A0, but the page size of your poster is not important as the posters will be presented digitally. However, if you are attending in-person and would like to bring along a physical poster, prepare your poster in A1 portrait format (59cm wide x 84cm long). Do not laminate your poster, or use heavy printing material.
- Naming your poster files: Name your poster files as follows: <your surname>-Oligo24-Poster.pdf, etc. For example, for David Jones, name your file as Jones-Oligo24-Poster.pdf. DO NOT name your poster files as, e.g., Oxford-poster, poster2024, Oxford-oligo-poster. Such files will be automatically rejected.
- Poster submission: Submit your final poster as PDF files via the link below no later than 15th March 2024. Late posters may not be included in the conference programme. Please DO NOT send your poster or abstract files by email. Please ensure you send us the very final version of your poster (as well as your poster abstract), as once published, it cannot be replaced.
Before uploading your poster, you must make sure that you follow ALL of the instructions above!
Poster presentation:
- Poster PDF files (required): Whether the presenter is attending virtually or in-person, poster PDF files are required, which will be made available via the secure conference documents page to the conference participants. The participants will be able to ask questions via the Zoom chatbox during the conference. There is no specific time for presenting digital posters.
- Flash-talk videos (optional): We are pleased to offer poster presenters the opportunity to prepare a short video presentation about their poster and send it before the conference. The videos will be made available on the LPMHealthcare YouTube channel. Below is further information for sending your video presentation.
- Give your presentation (no longer than 5 minutes) using Zoom or another platform of your choice.
- Convert the video into a format compatible with YouTube (e.g., MP4).
- Send your video to OligoOxford@gmail.com using a file transfer program, such as MailBigFile or WeTransfer.
- Hardcopy posters (optional): If attending in-person, you may bring along a printed copy of your poster (maximum A1 size) to be displayed during the conference. You may be assigned a specific day to display your poster.
- The participants can post their questions on Twitter at any time using the meeting hashtag #OligoOx24, as well as the poster specific hashtag (given under each poster abstract) – do tag @LPMHealthcare in your tweets.
- Any further information about the poster presentations at this digital meeting will be available in the future.
Before uploading your poster, you must make sure that you follow ALL of the instructions above!
(Presenters in Bold)
Accepted poster abstracts (Unedited) will be published below. 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 emailing OligoOxford@gmail.com.
New approaches for anti-cancer therapeutic interventions: development of “smart” self-sufficient RNA-silencing bioconjugates against highly oncogenic microRNAs
Cheuk Kit Cheung, David J Clarke, Elena V Bichenkova
Faculty of Biology, Medicine and Health, School of Health Sciences, Division of Pharmacy and Optometry, University of Manchester, Oxford Rd, Manchester M13 9PT, UK
This research involves the development of novel sequence-selective bioconjugates that links an antisense oligonucleotide to catalytic agents capable of cleaving biologically significant RNA molecules. Such sequence-specific artificial RNases do not rely on cellular machinery and are self-sufficient, which may provide a new platform for anticancer therapy with improved safety and effectiveness. MicroRNA-155, which is overexpressed in many types of cancer, including leukaemia, pancreatic cancer and breast cancer has been selected as the therapeutic target for this study. With the aim of exploring the cleavage activity of peptidyl-oligonucleotide conjugates (POCs) against MicroRNA-155, multiple structural possibilities of the conjugates have been designed, synthesized and tested against fluorescently labelled micro-RNA-155. The study begins with exploring the cleavability of different regions of MicroRNA-155 by varying the recognition motifs that allow the catalytic agents to be placed in close proximity to different regions of the target MicroRNA sequence. These POCs were tested with corresponding fluorescent assays designed in our group to expose the cleavable regions on the target. The new structural design involved the use of different sizes of bulge-loop in combination with a different number of catalytic peptides targeting a feasible target region previously discovered. Our next challenge is to explore different structural possibilities of the catalytic peptides by varying their amino acid compositions and sequences with the aim of identifying the most active catalyst in terms of RNA cleavage and thus enhancing the biological activity of the POCs. The possibility of incorporating LNA into the recognition motif has also been investigated to enhance the hybridisation power of POCs, which is particularly important for targeting relatively short (22-25 nucleotides) sequences of small non-coding regulatory microRNAs.
Approaches to the enzymatic synthesis of hypermodified DNA polymers and their application in development of modified aptamers
Marek Ondruš, Michal Hocek
Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo nam. 542/2, 160 00 Prague 6, Czech Republic
Enzymatic synthesis of DNA is well-established method but it is highly desired to develop versatile enzymatic approaches for hypermodified DNA composed exclusively only from base-modified
2´-deoxyribonucleoside triphosphates. Base-modified dNTPs open new possibilities to explore novel bio-physical and theranostic properties of modified DNA. Therefore, we designed and synthesized two series of all four hydrophobically-modified dNTPs and used them for enzymatic synthesis of hypermodified DNA as an example of sequence-specific functionalized polymer. Due to modifications, hypermodified DNA cannot be sequenced directly by common sequencing platforms. Therefore, we developed method for replication of hypermodified DNA into natural DNA which was then easily sequenced and provided information about fidelity of DNA polymerase. Moreover, we developed new beneficial alternative for enzymatic synthesis of modified single-stranded DNA from double-stranded hybrid duplex where template and non-modified primer were efficiently removed for their application on the characterization and development of modified nucleic acids aptamers. Nucleic acid aptamers are short sequence-specific ssDNA/RNA polymers able to bind a wide variety of targets via protein-nucleic acid interactions with affinity rivalling antibodies. Despite this, there is still a major challenge for binding to “undruggable” targets such as hydrophobic proteins. To address this problem, we are developing aptamers bearing hydrophobic moieties incorporating the best attributes of two types of biopolymers: huge conformational flexibility of ssDNA combined with diversity-enhancing protein-like moieties. We have successfully selected modified aptamer bearing hydrophobic modifications, such as the 7-phenylbutyl-7-deazaadenine-modified DNA aptamer resulting in high binding affinity for the Heat Shock Protein 70 (HSP70). This work was supported by Czech Science Foundation (EXPRO), 20-00885X.
A Click Chemistry Derived Di-nuclear Copper Artificial Metallonuclease
Simon Poole1,2, Obed Akwasi Aning3, Vickie McKee1,4, Pegah Johansson5,6, Georgia Menounou1, Joseph Hennessy2, Bríonna McGorman2, Creina Slator2, Fredrik Westerlund3, Andrew Kellett 1,2,*
1 Synthesis and Solid-State Pharmaceutical Centre, School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland
2 School of Chemical Sciences and National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland
3 Department of Biology and Biological Engineering, Chalmers University of Technology,
Gothenburg, Sweden
4 Department of Physics, Chemistry and Pharmacy University of Southern Denmark Campusvej 55, 5230 Odense M (Denmark)
5 Laboratory of Clinical Chemistry, Sahlgrenska University Hospital Gothenburg, Sweden
6 Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Sweden
The design of copper(II)-based metallodrugs with artificial metallonuclease (AMN) activity has been well reported in the literature as alternatives to current therapeutics. This work describes the development of an original di-nuclear Cu(II)-based small molecule, Cu(II)-BPL- C6, synthesised using a copper-catalysed azide-alkyne approach, that is capable of site-specific interactions and low micromolar cleavage with DNA. The complex is designed to induce DNA damage by coordinating two distal Cu(II) centres to the phenanthroline pendants at the extremes of the scaffold. DNA binding experiments revealed a predilection for polyd[(A-T)]2 over polyd[(G-C)]2 and ctDNA, established through circular dichroism spectroscopy, agarose gel electrophoresis and fluorescence quenching experiments. The oxidative cleavage mechanism of Cu(II)-BPL-C6 is elucidated using advanced in-vitro molecular and biophysical assays using spin trapping antioxidants and free radical scavengers. The quantification of genomic DNA oxidative lesions were monitored using peripheral blood mononuclear cells, which were exposed to Cu(II)-BPL-C6. Using fluorescently modified dNTPs and base excision repair (BER) enzymes, these lesions were characterised. NCI-60 screening reveals that Cu(II)-free BPL-C6 demonstrates a high degree of selectivity for melanoma, breast, colon and non-small cell lung and cancer cell lines. Overall, this research contributes to the development of a new innovative cancer therapeutic with potential application in the clinic.
Targeting Oncogenic miRNA-155 with Oligonucleotide-Peptide Conjugates: A Novel Strategy for Precision Cancer Therapy
Rodion Shipetin, David J Clarke, Elena V Bichenkova
Faculty of Biology, Medicine and Health, School of Health Sciences, Division of Pharmacy and Optometry, University of Manchester, Oxford Rd, Manchester M13 9PT, UK
MicroRNAs (miRNAs) play pivotal roles in the regulation of gene expression, with their dysregulation being a hallmark in various cancers. Oncogenic miRNA-155 has been identified as a key player in cancer progression, making it an attractive target for therapeutic intervention. Our research focuses on the development of novel therapeutic agents through the design, synthesis, and characterization of oligonucleotide-peptide conjugates that specifically target miR-155. The conjugates consist of an oligonucleotide segment that serves as a recognition motif for miR-155, conjugated with a peptide moiety that acts catalytically to cleave and degrade the target miRNA. This innovative approach aims to achieve high specificity towards the oncogenic target, potentially leading to cancer treatments that are more effective and exhibit fewer side effects compared to traditional chemotherapy. The synthesis of these conjugates involves a series of steps to ensure that the oligonucleotide and peptide components are correctly linked together and form functional ribonucleases against miRNA. We employed HPLC and 1D 1H NMR spectroscopy for the purification and characterization of the conjugates to confirm successful synthesis. By targeting miR-155 with such high specificity, these conjugates could minimize the off-target effects commonly associated with cancer treatments, thereby reducing the overall toxicity of chemotherapy. The development and characterization of oligonucleotide-peptide conjugates targeting miR-155 illustrate a promising strategy for enhancing the sequence-specificity, potency (due to catalytic turnover) and reducing the side effects of cancer treatments. While this approach is in its early stages, it suggests the potential for synergistic use with traditional chemotherapy, potentially improving patient outcomes by reducing toxicity. Our findings represent a step forward in the pursuit of more precise and less harmful cancer therapies.
New generation of RNA-targeting oligonucleotide analogues as a platform for development of innovative therapeutics against cancer: “smart”, responsive bioconjugates against oncogenic microRNAs
Fangzhou Shan, David J Clarke, Elena V Bichenkova
Faculty of Biology, Medicine and Health, School of Health Sciences, Division of Pharmacy and Optometry, University of Manchester, Oxford Rd, Manchester M13 9PT, UK
Peptidyl-oligonucleotide conjugates (POCs) represent a type of artificial RNases with high sequence-specificity and cleavage efficiency. They hold promise as a future therapeutic platform to target oncogenic microRNAs (oncomiRs) in a sequence-specific manner, while ensuring both biosafety and efficacy. microRNAs, approximately 20-25 nucleotides in length, play important roles in regulating gene expression, cell proliferation, differentiation, and apoptosis in cells. Decades of research have shown that cancer cells often show abnormal expression profiles of oncomiRs, such as miR-17 (found in lung, lymphoma, and breast cancer) and miR-21 (e.g., lung, breast, colorectal cancers), which are often overexpressed. Our recent studies have shown that POCs can effectively catalyze and cleave target miRNAs in vitro, while in vivo experiments in animals have demonstrated their tumor-suppressing effects. However, the complexity of their interactions with the complementary miRNA targets has never been studied before. This research is focused on the computational modelling of RNA cleavage by these artificial enzymes within multiple complex configurations. Our insights into the dynamics of the RNA cleavage offer the opportunity to optimize the recognition motifs and catalytic domains of such artificial ribonucleases to improve their potency and catalytic turnover.Given the complexity of these macromolecular systems, our team has developed a set of molecular models through molecular simulations using Mathematica 13.2. Mathematical modelling of heteroduplexes between the target miRNAs and POCs allowed us to analyze the set of available experimental data on RNA cleavage to explain dynamics of miRNA degradation and improve their future experimental design. Building on the optimization of recognition motifs, the next challenge for our team is to enhance the biological activity of POCs molecules by improving the composition and sequence of catalytic peptides.
Probing the recognition site of hydrophobic 7-phenylbutyl-7-deazaadenine-modified HSP70 DNA aptamer and its dependence of modified nucleobases
Pablo Alberto Franco Urquijo, Marek Ondruš, Michal Hocek
Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo nam. 542/2, 160 00 Prague 6, Czech Republic
Aptamers, short sequence-specific RNA or single stranded DNA (ssDNA) that binds to their cognate target are selected by in vitro systematic evolution of ligands by exponential enrichment (SELEX) from randomized oligonucleotide pools. Typically, natural nucleotide libraries constrain the available chemical diversity resulting in a lower structural repertoire for target interactions. To overcome this, libraries with enhancing protein-like moieties have been produced that include a range of chemical modifications conferring advantages such as increased affinity, specificity and aptamer expanded epitopes. Between this modifications, hydrophobic modifed libraries have been promisingly used for “undruggable “proteins resulting in an improved success rate and novel functionalities. Within the hydrophobic modified libraries used for SELEX, the 7-phenylbutyl-7-deazaadenine-modified DNA aptamer selected via PEX and magnetic bead-based SELEX resulted in high affinity and specific aptamers to the Hsp70 protein. Modified aptamers displayed low nanomolar range KD compared with their natural counterpart (>5 µM) demonstrating the importance of its hydrophobic modification for their binding affinity. Due to this, the impact of the chemical modification with its target and the minimal binding sequence is being tested. Modified truncations were produced by an alternative enzymatic synthesis of modified ssDNA obtained from double-stranded (RNA-DNA) hybrid duplex. By this approach, the minimal binding sequence is being determined. In addition, flexibility and length of the linker connecting the modification and their impacts on the binding properties are being tested. By using this post-SELEX modification approach, we aim to improve the performance of the previously selected aptamer and get a deeper insight about the importance of the hydrophobic moieties for their binding properties.
This work was supported by Czech Science Foundation (EXPRO), 20-00885X.
Therapeutic Aptamer Targeting Dickkopf-1 for Triple Negative Breast Cancer Therapy
Ziqi Chen1,2,3, Sifan Yu2,4, Yihao Zhang2,4, Yufei Pan2, Xin Yang1,2,3, Chi Ho Chan1,2,3, Hang Yin Chu2,4, Yuan Ma1,2,3, Meiheng Sun1,2,3, Fangfei Li1,2,3, Bao-Ting Zhang2,4, Aiping Lu1,2,3, Ge Zhang1,2,3, Yuanyuan Yu1,2,3
1Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases (TMBJ), School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China
2Guangdong-Hong Kong-Macao Greater Bay Area International Research Platform for Aptamer-based Translational Medicine and Drug Discovery (HKAP), Hong Kong SAR, China
3Institute of Systems Medicine and Health Sciences, Hong Kong Baptist University, Hong Kong SAR, China
4School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
Triple-negative breast cancer (TNBC) is a highly aggressive and challenging malignancy characterized by the absence of direct therapeutic receptors, resulting in limited systemic treatment options. Prognostic marker Dickkoff-1 (DKK1) has been associated with distant metastasis and low overall survival in different cancer patients. Our research revealed significantly elevated mRNA levels of DKK1 in TNBC patients compared to other patients, with higher protein expression in TNBC tumor tissues than in normal tissues. These findings highlight DKK1 as a potential therapeutic target for TNBC treatment. However, while a therapeutic antibody targeting extracellular DKK1 showed some inhibition of tumor progression, its effectiveness was limited. Our research demonstrated the crucial role of intracellular DKK1 in tumor progression. Through genetically knockdown and knockout of DKK1, we observed significant inhibition of proliferation, migration and invasion in TNBC cells. Based on this finding, we identified a high affinity and active aptamer specifically targeting DKK1. Notably, this aptamer could be internalized into TNBC cells via endocytosis without the need for lipid nanoparticles. Furthermore, by targeting intracellular DKK1, we effectively supressed the proliferation, migration and invasion of TNBC cells in vitro, and inhibited the tumor growth in TNBC mice in vivo. This work introduces a novel therapeutic strategic for TNBC treatment, utilizing aptamers to target intracellular molecular targets. This study was supported by the Hong Kong General Research Fund from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. 12102120.; Project No. 12102322), Theme-based Research Scheme from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. T12-201/20-R), and Inter-institutional Collaborative Research Scheme from Hong Kong Baptist University (Project No. RC-ICRS/19-20/01).
