A Comprehensive Supramolecular Approach for an RNA vaccine for Influenza A (H1N1)

Project Information

SupraRNA

Grant agreement ID: 897666

DOI

10.3030/897666

Project closed

EC signature date 11 March 2020

Start date 1 May 2020

End date 30 June 2022

Funded under

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Total cost

€ 212 933,76

EU contribution

€ 212 933,76

Coordinated by

THE UNIVERSITY OF BIRMINGHAM
United Kingdom

Periodic Reporting for period 1 - SupraRNA (A Comprehensive Supramolecular Approach for an RNA vaccine for Influenza A (H1N1))

Reporting period: 2020-05-01 to 2022-04-30

Summary of the context and overall objectives of the project

Influenza is a contagious respiratory illness caused by influenza viruses. These viruses have several types (namely A, B and C), which are rapidly changing, and in severe cases can result in hospitalization or death. In India, since 2009, the influenza A H1N1 variant has caused many deaths each year and is an ongoing health concern. Vaccines are available against influenza, but are expensive and their slow production means they cannot be produced fast enough to protect against each mutation of the disease. A new type of vaccine based on nucleic acids, DNA and RNA, show promise for overcoming this problem, as they can be more rapidly produced to prevent or treat pathogens that are rapidly evolving, and have lower production costs. However, the bare DNA is prone to degradation in the body, which will limit its effect and application in the clinic. To overcome this challenge Dr. Sikder has been developed supramolecularly assembled nanoparticles for the safe delivery of nucleic acid vaccine with ultimate target to make silence H1N1 virus gene.

Further the knowledge gained has paved the way for DNA/RNA vaccines against other diseases to be developed in the future.

Overall, this proposal aims to lay the groundwork for extending the scope of nucleic acid vaccines by exploring the potential of supramolecular assemblies as a delivery vector. A series of π-amphiphiles have been synthesized to prepare supramolecularly assembled nucleic acid delivery system for the vaccination of influenza A H1N1 strain. The central π-amphiphile moiety has been functionalized with the nucleic acid strand via a redox responsive disulfide bond, and hydrophilic oligo-oxy aryl groups connected via a hydrogen bonding unit to promote self-assembly. Steric stabilization has been afforded to the surface decorated nucleic acid nanoparticles to protect from enzymatic hydrolysis in the complex biological environments, through co-assembly with an analogue π-amphiphile which has been alternatively decorated with poly(ethylene glycol) (PEG) chains. The therapeutic efficacy of the nano-assembly has been evaluated through transfection efficacy in macrophage cell lines.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Dr. Sikder has successfully developed a nucleic acid delivery system using supramolecular assembly of π-amphiphiles. Work performed and results obtained so far: i) Synthesis of different π-amphiphiles; ii) characterization of the amphiphiles; iii) Evaluation of their self-assembly and co-assembly; iv) Glutathione responsive nucleic acid delivery.

Dr. Sikder has presented her results at various national and international conferences (American Chemical Society (ACS) Fall 2021 (Poly division), “Biomaterials Translation Workshop 2022, Recent Appointees in Polymer Science-2021, RSC Virtual Macrocyclic and Supramolecular Chemistry Seminar) as well as at the regular meetings organized by the polymer, supramolecular and biological chemistry communities (ECR MASC Meeting 2022, Mcbain Medal Symposium, PERCAT Postdoctoral Researcher Conference 2021). This has helped Dr. Sikder to further collaborate in future with scientific leaders and has increased her contacts.

For the initial few months of the of the project starting date, COVID-19 pandemic caused most of the planned dissemination results and activities to be cancelled or postponed. To make effective use of the time under lockdown, Dr. Sikder has worked on a review article and was published in ACS Applied Polymer Materials. Further a paper on preparation of diverse supramolecular nanostructure by utilising various non-covalent interactions has been published in Nanoscale. All the research article was made available as open access (OA) article. Another review on preparation of self-assembled nanoparticles has been written and published in 'Accounts of Chemical Research'. EU funding has been acknowledged in all the public engagement activities undertaken during the period of the fellowship, as well as in the publications that are published and those that are currently about to be published.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Dr Sikder is well trained in organic chemistry and especially in synthesis, as well as supramolecular self-assembly of organic dyes. These skills have brought to the UK host University, providing a new area that the host group has gained experience in. This extensive synthetic and supramolecular assembly experience is complementary to the polymer synthesis and characterisation experience of the UK group. Hence, Dr Sikder’s involvement in the group has offered new direction and opportunity for the preparation and design of their nanostructured assemblies.

Together, this research proposal is expected to make impact on the UK research community in the area of drug delivery, specifically in efficient synthesis and self-assembly of fluorescent nanostructures. Particularly the combination of expertise of the fellow and UK host has allowed for research advances which can add to the existing knowledge base and inspire novel approaches to treatments. Particularly, the exploration of nucleic acid delivery for vaccinations has provided a new research direction in the UK group, and influence current projects towards real-world applications.

Further, this partnering of international excellence has supported the development of a well-trained research community and further raise the profile of emerging leaders in Indian polymer science. By undertaking this research project at the University of Birmingham, a recognized world-leader in materials science, Dr. Sikder has participated in research at the frontier of the field and have accessed to some of the best equipment (and technical support) in the world for polymer synthesis and analysis. The fellow will bring back to India this precious research experience and also the new networks formed through this fellowship, to inspire others and also shape her future career.

Scheme for supramolecularly assembled DNA-nanoparticles and corresponding targeted delivery