Day 1 – June 9
Lectio Magistralis
Fernando Albericio – University of KwaZulu-Nata and University of Barcelona
Solid-Phase Peptide Synthesis (SPPS): Integrating Resins, Protecting Groups, and Coupling Reagents in an Optimal Solvent
Between 2016 and 2024, the U.S. Food and Drug Administration (FDA) approved 33 peptides, accounting for 8.1% of all drugs authorized during this period. The structural characteristics of these peptides differ significantly from those approved in earlier years. Modern peptides often feature (bi)cyclic structures, increased molecular size, non-proteinogenic amino acids, and modifications such as polyethylene glycol (PEG) or fatty acid conjugation. Additionally, the large-scale production of some peptides, often requiring multi-kilogram quantities, presents significant manufacturing challenges.
The widespread availability of peptide therapeutics today would not have been possible without the ground-breaking work of Nobel laureate R. Bruce Merrifield, who pioneered Solid-Phase Peptide Synthesis (SPPS) in the 1960s. Since its inception, SPPS has evolved substantially to meet the growing demand for peptides while addressing challenges related to efficiency, scalability, and sustainability.
At its core, SPPS involves the use of solid supports (resins), protecting groups, and coupling reagents in an appropriate solvent system. This presentation will highlight contributions from my laboratory toward advancing peptide chemistry in alignment with sustainability principles.
Keynote – Plenary speech
Sudhir Agrawal – Arnay Sciences
Development of RNA Therapeutics: Evolution Over Three Decades
RNA therapeutics have emerged as a well-established platform for drug discovery and development, featuring approved drugs that employ various mechanisms of action. Over the past three decades, many lessons have been learned about these classes of compounds as drugs (1). Chemical engineering has played a crucial role in imparting drug-like properties to oligonucleotides, with gapmers and modified RNA antisense being commonly used in approved antisense drugs. Evidence gathered over the years indicates that protein binding and interactions with pattern recognition receptors have led to off-target activity for oligonucleotides. To address these concerns, we have explored oligonucleotide shapes that bring the 3′ and 5′ ends together into transient cyclic structures. Various types of cyclic structures have been developed and evaluated (2). These cyclic structures demonstrate reduced protein binding and interactions with pattern recognition receptors, enhancing antisense delivery, specificity, and potency. These designs can be broadly applied to different mechanisms of action associated with RNA therapeutics.
OLIGONUCLEOTIDES
Day 2 – June 10
Troels Koch, Vikash Reebye – MiNA Therapeutics, Keynote speech
RNA Activation: Concept and Clinical Application
RNA activation (RNAa) is a pivotal pillar in RNA therapeutics, complementing antisense oligonucleotides (ASOs), siRNA, and mRNA therapies. The presentation chronicles MiNA Therapeutics’ groundbreaking journey from laboratory discovery to clinical implementation, highlighting the development of the world’s first RNAa therapeutic to enter clinical trials for advanced liver cancer.
The path to clinical application required significant challenges in delivery, stability, and potency that shaped the evolution of this novel therapeutic approach. The biological perspective, exploring RNAa’s vast potential across multiple disease states and its unique contribution to personalised medicine for addressing unmet clinical needs will be presented.
We will also show novel medicinal chemistry insights, examining the mechanistic distinctions between structurally similar siRNA and small activating RNA (saRNA/RNAa) molecules that produce remarkably different biological outcomes. This analysis will illuminate how strategic modifications can dramatically enhance RNAa drug potency, revealing the scientific principles that underpin this emerging therapeutic class.
By demonstrating how the diverse modes of action specific to different RNA modalities create unprecedented opportunities for targeted therapies, this presentation offers a comprehensive overview of RNAa’s position within the expanding RNA therapeutics landscape.
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Giacomo Padroni – CPI
Acceleration of oligonucleotide process development via machine learning
The number of approved short synthetic oligonucleotide therapeutics is sharply rising and with it, increased challenge to develop sustainable manufacturing strategies.
One of the key obstacles in optimising Solid Phase Oligonucleotide Synthesis (SPOS) is the precise control of numerous variables (~30) required to prevent the formation of complex and unwanted impurities. The effort and time required to understand each step of the optimisation process and identify critical impurities is considerable.
In this presentation, we demonstrate the integration of the advanced machine learning platform Alchemite™ (Intellegens) to oligonucleotide process optimisation, with the goal of reducing development time and cost while improving synthesis quality and yield.
In this work, our approach leverages adaptive machine learning (ML)-guided Design of Experiment (DoE) to optimise the synthesis of three unique oligonucleotides while developing a custom oligonucleotide manufacturing software extension for Alchemite™. This extension enables automated upload of synthesis and analytical data with minimal user input. Additionally, Alchemite™ has been equipped with an impurity identification logic that identifies potential impurities based on the input oligonucleotide sequence and mass spectrometry data, significantly reducing analysis time and simplifying interpretation. Finally, we show how our training data can be used to explore conditions to improve both yield and overall purity of a new oligonucleotide sequence.
The final version of the software feature extension will predict process impurities and degradation products for oligonucleotides based on the sequence and process parameters, automating the initial phases of oligonucleotide process development. This will streamline tech transfer, improve product yield, reduce experimental time and ultimately, minimise waste, while managing cost-effectiveness.
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Xavier Gerard – Thermo Fisher Scientific
Perspectives on impurities in phosphoramidites; creating meaningful specifications
There is an emerging need to enhance the understanding of phosphoramidite impurities for oligonucleotide therapeutics, with a particular emphasis on non-critical impurities. The influx of new CDMOs and drug developers has revealed a tendency to minimize impurity categorization—often misclassifying or omitting chain terminating and non-critical impurities—which may lead to unnecessary over-processing of phosphoramidites. An in-depth evaluation of phosphoramidite impurities is therefore essential to develop more nuanced and sustainable specifications through the lens of new regulatory guidance.
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Jale Muslehiddinoglu – ST Pharm
Process Development Strategies for an Evolving Oligonucleotide Landscape
Oligonucleotide therapeutics have evolved from early single-stranded antisense oligonucleotides to siRNA and beyond, incorporating increasing structural complexity and chemical modifications to enhance efficacy, stability, and delivery. As their use expands beyond rare diseases to more widespread diseases, the demand for larger-scale production has grown, requiring manufacturing strategies that balance efficiency, scalability, quality, and cost.
Process development strategies have adapted to meet these evolving demands, addressing greater molecular complexity, diverse chemical modifications, and varying oligonucleotide lengths while ensuring safety and reproducibility. Advances in process analytical technology, modeling, automation, digitalization, and engineering principles are shaping the future of scalable, high-quality, and cost-effective oligonucleotide manufacturing. This presentation will highlight how these advancements are shaping the next generation of oligonucleotide process development.
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Ruben Godwin-Suttie – AstraZeneca
Establishing an internal oligonucleotide process development capability at AstraZeneca
In recent years, AstraZeneca’s clinical oligonucleotide portfolio has continued to grow, in terms of both the number of projects and their technical complexity. To meet the demands of this evolving portfolio AstraZeneca’s early-phase development
organisation (Pharmaceutical Sciences) triggered an expansion plan to create a dedicated internal capability for early phase oligonucleotide process development. The intention of this new capability was to ensure that AstraZeneca could deliver value-adding impact to the early development phase, improving key metrics such as delivery timelines, environmental impacts and overall costs whilst still ensuring security of supply for the expanding portfolio.
To achieve these goals, the new development capability would be required to cover the entire oligonucleotide workflow, from synthesis and purification to annealing and conjugation, with full analytical support. This capability uplift will enable AstraZeneca to better share practical results and scientific understanding with CDMOs, ultimately driving improvements in manufacturing.
In this presentation, we will describe our progress over the last 12 months from the initial setup of the lab to our first phase of implementation and will detail the various aspects such as equipment selection, ways of working, early results and analytical collaboration that have been employed to achieve this.
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Daisuke Takahashi – Ajinomoto
Advanced siRNA Manufacturing: Hybrid Enzymatic and Liquid Phase Synthesis Approach AJIPHASE®
Traditional oligonucleotide including siRNA manufacturing methods often encounter significant challenges in terms of cost, efficiency, and scalability. To overcome these hurdles, we have developed a pioneering enzymatic ligation approach combination with AJIPHASE® solution-phase synthesis as a hybrid strategy. This innovative approach not only improves production yield and purity but also ensures greater sustainability.
In this presentation, we will explore the mechanics of our hybrid method, illustrating how the integration of enzymatic ligation and solution-phase synthesis provides a robust and cost-effective alternative to solid-phase techniques. With a focus on large-scale production, we will share empirical data demonstrating the hybrid method’s effectiveness in achieving high yields and purities consistently.
Our presentation will further delve into the practical aspects of quality control and scalable manufacturing, underlining how our approach meets industry standards while reducing overall production costs.
By addressing these critical factors, we aim to highlight the tangible benefits and future potential of this advanced manufacturing strategy for siRNA, setting a new benchmark in the field for industrial-scale applications.
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Audrey Robic – Allozymes
Advancing Chemoenzymatic Oligonucleotide Synthesis Through Engineered Ligases
Allozymes is developing enzyme-based technologies to address key limitations in traditional oligonucleotide synthesis, including high production costs, scalability constraints, and inefficiencies in assembling longer or structurally complex sequences.
The company is advancing a hybrid chemoenzymatic approach that integrates enzymatic ligation with conventional chemical synthesis. Central to this strategy is the engineering of a panel of ligases optimized for oligonucleotide assembly. In this presentation, we will describe the engineering and functional characterization of ligases suitable for oligonucleotide assembly, and demonstrate how their integration into a hybrid synthesis workflow can improve overall yield, reduce cost, and enable scalable synthesis of short, long, and chemically modified RNA sequences.
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Elena Kumm – Tosoh Bioscience
Therapeutic Nucleic Acids – Advanced Solutions for Analytics and Downstream Processing
The rapid growth of oligonucleotide-based therapeutics has brought new challenges in purification and analytical characterization, particularly due to their structural complexity and diverse impurity profiles. In this presentation, we explore the latest advancements in chromatographic techniques tailored specifically for therapeutic oligonucleotides. We will discuss how to select and optimize strategies to effectively address different classes of impurities, from short- and longmers to process-related contaminants. With case studies as practical applications of these approaches, we are highlighting innovative solutions that improve both efficiency and product quality. Join us for a deep dive into how chromatography is evolving to meet the demands of next-generation oligonucleotide therapeutics.
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Andrew Livingston – Exactmer
Liquid phase oligonucleotide synthesis by Nanostar Sieving – taking aim at large-scale, sustainable manufacturing of oligonucleotides
Exactmer have developed a new platform technology, Nanostar Sieving, for sustainable manufacturing of oligonucleotides, fully in liquid phase. This innovative technology consists of a multi-branched hub (the “Nanostar”) dissolved in solution, to which monomers are added iteratively, forming oligonucleotide polymers. At each iteration, the reaction debris is removed from the growing Nanostar by diafiltration, using Exactmer’s highly selective organic solvent stable membranes for molecular “sieving”, until the full-length oligo sequence is produced. The oligo is then cleaved from the support, isolated and purified. Nanostar Sieving is a completely liquid phase process which does not require a solid support, precipitation or extraction steps. The synthesis process is carried out in a single solvent or single solvent mixture, does not use halogenated acids or halogenated oxidants, and is fully automated. In-process controls minimise the use of phosphoramidites (typically 1.2 equivalents) and reagents, including the detritylation acid, and the process can complete up to 3 full cycles in a day. The highly selective membranes are manufactured at large scale by Exactmer, in spiral wound module format. Nanostar Sieving has been used to produce full-length oligonucleotides or oligo fragments at the 10-20 mmol scale. Both will be described in the presentation which will detail the results for syntheses. Nanostar Sieving offers simplification of chemical oligo synthesis and reduces the process mass intensity through lower reagent use. Extensions currently being researched include solvent recycling, acid-free protecting group strategies and the use of greener reagents.
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David Butler – Hongene Biotech
Chemoenzymatic ligation technology comes of age: A present-day solution for scalable manufacturing for siRNA and sgRNA drugs
As demand accelerates for siRNA therapeutics targeting common disease indications and for high-quality sgRNA to support gene editing, manufacturers are under increasing pressure to scale production all the while improving cost efficiency, quality, and sustainability. Chemoenzymatic ligation of oligonucleotide fragments—Generation 2 manufacturing technology—offers a transformative alternative to overcome limitations of traditional solid-phase oligonucleotide synthesis (SPOS, Generation 1 manufacturing technology).
In this presentation, we present Hongene’s latest advancements in Generation 2 technology for oligonucleotide manufacturing. We begin with a technical overview of our unique ligation approach, highlighting its features including improvements in quality, scalability, sustainability, and enablement of synthesis of long and complex sgRNA. We will also showcase a key internal milestone: the successful manufacture of a 1 kg GMP batch of siRNA via ligation, marking a major step toward meeting future clinical and commercial demand.
Transitioning from Generation 1 to Generation 2 manufacturing technology presents huge upside for oligonucleotide drug developers. We will discuss CMC and regulatory considerations for clinical development using Generation 2 processes that will underscore our conviction that ligation is not just a future technology – it’s a present-day solution ready for broad adoption.
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Afaf El-Sagheer – University of Southampton
Neutral backbones for oligonucleotides enhanced gymnotic delivery
Artificial DNA backbones have potential in therapeutics and synthetic biology (1-12) with the hypothesis of the ability of these modifications in mimicking the native phospahate backbone. These results provide insights into the design of biocompatible backbone mimics that could be used in the assembly of large, modified DNA and RNA constructs and used in various therapeutic applications (13-16).
We developed a synthetic route to construct potentially therapeutic oligonucleotides containing uncharged LNA-amide linkages. The chemistry has the potential to be automated and carried out at scale for therapeutic oligonucleotide development. These new constructs have high resistance to enzymatic degradation and bind to complementary RNA with affinity and selectivity superior to unmodified ONs. In studies with gymnotic (naked) delivery, combining LNA-amides with phosphorothioates improves cell uptake. Poor cellular uptake is currently a major barrier in oligonucleotide therapeutics and combining the PS and LNA modifications with charge-neutral amide backbones could lead to improved clinical efficacy (12).
Very recently we simplified the chemistry and made oxyamide, sulfamate/sulfamide neutral backbones (17-18) in therapeutic oligonucleotides and showed great gymnotic delivery in biological systems.
References and notes
1. A. H. El-Sagheer and T. Brown, J. Am. Chem. Soc. 2009, 131, 3958.
2. A. H. El-Sagheer and T. Brown, Proc. Natl. Acad. Sci. U. S. A. 2010, 107,15329.
3. H. El-Sagheer, A. P. Sanzone, R. Gao, A. Tavassoli and T. Brown, Proc. Natl. Acad. Sci. USA, 2011, 108, 11338-11343.
4. A. Dallmann, et al., Chemistry – A European Journal, 2011, 17, 14714-14717.
5. A. H. El-Sagheer and T. Brown, Chem. Commun., 2011, 47, 12057-12058.
6. X. Chen, A. H. El-Sagheer and T. Brown, Chem. Commun., 2014, 50, 7597-7600.
7. A. H. El-Sagheer and T. Brown, Chem. Sci., 2014, 5, 253-259.
8. C. N. Birts, et al., Angew. Chem. Int. Ed., 2014, 53, 2362-2365.
9. A. Shivalingam, A. E. S. Tyburn, A. H. El-Sagheer and T. Brown, J. Am. Chem. Soc., 2017, 139, 1575-1583.
10. M. Kukwikila, N. Gale, A. H. El-Sagheer, T. Brown and A. Tavassoli, Nat. Chem., 2017, 9, 1089–1098.
11. A. H. El-Sagheer and T. Brown, Chem. Commun. 2017, 53, 10700-10702.
12. Y.R. Baker, et al. Nat. Commun., 2022,13, 4036.
13. L. Taemaitree, A. Shivalingam, A. H. El-Sagheer and T. Brown, Nat. Commun., 2019, 10, 1610.
14. L. Taemaitree, A. Shivalingam, A. H. El-Sagheer and T. Brown. Methods in Molecular Biology, 2162, 2021
15. S. Epple, et al. J. Am. Chem. Soc., 2021,143, 39, 16293–16301.
16. A. Shivalingam, L. Taemaitree, A. H. El-Sagheer, and T. Brown, T., 2020, Angew. Int. Ed. 59, 11416-11422.
17. B. Zengin Kurt, D. Dhara, A.H. El-Sagheer, T. Brown, Org. Lett., 2024, 26, 4137.
18. D. Dhara, A.C. Hill, A. Ramesh, M.J.A. Wood, A.H. El-Sagheer, T. Brown, 2024, J. Am. Chem. Soc., 146, 29773.
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Day 3 – June 11
Hagen Cramer – Quralis, Keynote speech
Points to consider when preparing for oligonucleotide-based regulatory submissions
The talk will give guidance on how to work with CMOs and CROs from development through GMP manufacturing to ensure filing readiness. It will give advice on how to prepare for IND/IMPD regulatory submissions as regulatory expectations have changed over time.
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Tobias Pöhlmann – XNA Pharma
A peptide-siRNA prodrug approach to induce cell-specific RNAi
The selective induction of RNAi in target cells using therapeutic siRNA remains a major challenge for cancer therapy. Systemic injection of formulated siRNA drug
candidates usually leads to liver overload and side effects. Some delivery approaches aim to transport the payload to specific cells in order to increase the amount of oligonucleotide reaching the cancer target tissue, but still leading to high amounts in non-target tissue.
In contrast to a specific delivery approach to induce cell specific RNAi, we investigated a prodrug strategy: A short peptide was coupled to the sensitive 5`end of a siRNA antisense strand in order to inhibit siRNA function. The peptide contains a cleavage site for a protease with specific activity in cancer target cells, leading to peptide cleavage and cell specific siRNA activation. In non-cancerous cells, however, the peptide-siRNA prodrug remains inactive and is not able to induce RNAi. Proof of concept has been demonstrated in various cancer types, including breast and ovarian cancer in combination with several delivery strategies including LNPs and polymer-based nanoparticles. In vivo after systemic injection of LNP formulated peptide-siRNA, drug compounds were still found in high amounts in non-target tissue, but not leading to gene silencing, whereas in xenotransplant tumors induction of RNAi was observed. In the last months, peptide-siRNA manufacturing process was scaled-up in preparation for GMP manufacturing.
We believe that the peptide-siRNA prodrug strategy can significantly reduce side effects of therapeutic siRNAs in non-target tissues and explore new concepts for siRNA targets and sequence design.
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Ajay Kumar Singh – Dupont
High-loading anion exchange resin for oligonucleotide purification
Oligonucleotide therapeutics purification relies heavily on preparative-scale chromatography. Reverse phase high performance liquid chromatography (RP-HPLC) and anion exchange chromatography (AIEX) are the most widely employed techniques. The presentation provides an overview of DuPont™ AmberChrom™ resins which are highly compatible with the purification of various oligonucleotide modalities. It introduces a new AIEX resin functionalized with a strong anion exchanger group and compares its performance to other resins.
With positively charged functional groups, AIEX resins separate negatively-charged oligos and impurities based on sequence length and overall charge. The study includes an evaluation of the properties of the new agarose-based resin as well as its purification performance with crude antisense oligonucleotide feeds. The resin shows resolution and purification performance comparable to other resins used in this space with a uniquely high loading capacity. This feature is shown to result in more concentrated fractions during elution. These results, along with lower pressures at high flow rates, demonstrate that the new resin can be used for efficient high-throughput oligonucleotide purifications, and more broadly for the purification of negatively charged biomolecules.
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Tsuyoshi Yamamoto – Liid Pharmaceuticals
BROTHERSTM: A Proprietary Antisense Oligonucleotide Platform Unlocking New Therapeutic Horizons
Antisense oligonucleotides (ASOs) offer a powerful therapeutic approach by precisely binding to target RNA through Watson-Crick base pairing, enabling effective regulation of gene expression. Their rapid drug development potential through sequence optimization makes them a promising modality for addressing unmet medical needs. However, as clinical development progresses, safety concerns have emerged, particularly regarding systemic and central nervous system (CNS) toxicity.
Off-target effects, including unintended interactions with proteins and hybridization with non-target RNAs, are recognized as primary contributors to these safety issues.
To address this challenge, we have developed BROTHERSTM (BRO), a proprietary antisense oligonucleotide platform utilizing DNA nanotechnology to minimize off-target interactions while preserving ASO activity. The core innovation of BRO lies in its unique “ brother strand (BS)”, a specially designed complementary strand that leverages the non-equilibrium thermodynamics of ASOs to suppress two major off-target mechanisms simultaneously. This approach effectively reduces non-specific protein binding and unintended RNA interactions, thereby enhancing the safety profile of ASOs.
Previous studies have demonstrated that BRO significantly reduces systemic toxicity(1). In this presentation, we will introduce our recent findings highlighting BRO’s ability to mitigate CNS toxicity while maintaining therapeutic efficacy. These results open new avenues for the development of BRO-based therapeutics for intractable CNS diseases.
References and notes
1. Terada C. and Yamamoto T., et al. «Dynamic and static control of the off-target interactions of antisense oligonucleotides using toehold chemistry.» Nat Commun 14, 7972 (2023).
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Jennifer Frommer – University of Oxford
Evaluating Antisense Oligonucleotide Conjugation Patterns and Chemistries
Antisense oligonucleotides (ASOs) have become a cornerstone of medical research, offering a powerful approach to treating genetic diseases by targeting disease-affected RNA regions. Oligonucleotide sequences are easily programmable, chemically modifiable, and relatively inexpensive to produce, making them promising therapeutic candidates for a wide range of diseases, including neurodegenerative disorders (1).However, the delivery of ASOs remains a significant challenge (2), as they must effectively reach and enter target cells to perform their function.
The site-specific introduction of conjugates has the potential to enhance ASO biodistribution (3) and facilitate interactions with cell surface receptors and transporters, improving cellular uptake. In this work, we identified a range of biomolecules that can be incorporated during or after solid-phase synthesis, allowing us to explore various conjugation patterns. After optimising the synthesis and conjugation conditions, we successfully produced conjugated ASOs in high yields. Preliminary performance assessments of these conjugated ASOs were conducted in various cell types, utilising transfection and gymnotic uptake methods. Notably, mouse cell lines were included to ensure translational relevance for in vivo applications, alongside human cell lines.
Our findings demonstrate the feasibility of optimising ASO conjugation for improved delivery, with potential implications for advancing ASO-based therapies. Ongoing studies will focus on further refinement of these conjugation strategies and the evaluation of their efficacy in animal models, paving the way for clinical applications.
References and notes
1. Nature Reviews Drug Discovery, 2020, Vol. 19, 673–694.
2. ACS Nano, 2024, Vol. 18, 8, 6186–6201.
3. Nucleic Acids Research, 2019, Vol. 47, 12, 6029–6044.
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Judy Carmody – Carmody QS
Mitigating Risk in Drug Development Using AI
The pharmaceutical industry faces significant challenges in drug development, particularly in managing the risks associated with long timelines, high costs, and uncertain clinical outcomes. This presentation explores how artificial intelligence (AI) can play a pivotal role in mitigating these risks by enhancing decision-making, optimizing clinical trial designs, and improving predictive models. We will discuss real-world GMP and GCP examples of AI applications. Through these insights, this presentation aims to demonstrate how AI is transforming the landscape of drug development and driving more efficient, cost-effective, and safer pathways to bringing new treatments to market.
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Daniele Addis – Axolabs
Exploring Traut’s reagent as a versatile bifunctional linker for oligonucleotide conjugates
Oligonucleotide conjugates comprising ligands such as carbohydrates (e.g. GalNAc or mannose units), cholesterol and various other lipids, peptides and antibodies etc. represent a widely investigated approach aiming for increased cellular uptake, targeted
delivery to cells, bioavailability and hence overall efficiency of therapeutic nucleic acids (TNAs). In this context, linkers anchoring oligonucleotides with the specific ligands help in selective delivery and accurate release of the TNA payload at the target site.
In this project, oligonucleotide conjugation using traditional Traut’s reagent as a bifunctional linker is presented. Although well reported, its application in TNA-conjugation has been limited. The study illustrates the reagent’s role as a bridge between any amino-linker modified oligonucleotide and a molecule with a primary or secondary amine.
Conjugants with primary or secondary amines are in situ functionalized with a maleimide-equipped crosslinker. The second reactive handle is a primary amine installed in the oligonucleotide which is activated by 2-iminothiolane to form free-SH modified oligo, which in situ readily undergoes Michael addition to the former maleimide ring-conjugants via a thioether. Traut’s reagent can also react with a primary amine and a primary or secondary amine activated via succinimidyl 3-(2-pyridyldithio)propionate (SPDP) or similar groups to form a disulfide bridge. The maleimide reactive handle or the activated disulfide (e.g., SPDP) can be utilized to functionalize the oligonucleotide while the Traut’s reagent activates the primary amine on the conjugates. An advantage of this method is that, in the case of protein conjugation, the newly formed amidinium bond has a similar pKa to the original primary amine (e.g., lysine) of the unconjugated protein. This method simplifies and accelerates the multistep conjugation process and reduces the time and cost of conjugating a TNA with various conjugants such as lipids, PEGs, fluorophores, peptides, proteins, carbohydrates, especially where suitable reciprocity of conjugation pairs is not readily available.
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Sritama Bose – Nucleic Acid Therapy Accelerator (NATA)
Thiol-specific novel linkers for oligonucleotide conjugation
Chemical conjugation of oligonucleotides with molecular transporters is a key strategy to enhance their intracellular delivery and therapeutic efficacy. A critical requirement for this approach is the use of biologically stable linkers
