Generation of Aptamer-Molecularly Imprinted Polymer Hybrid Materials

Lead Research Organisation: The Open University
Department Name: Life, Health & Chemical Sciences

Abstract

Molecular recognition (the ability to specifically recognise a chemical compound) is a highly important feature of analytical science. More often than not compound specific recognition comes from biological element such as enzymes, antibodies and DNA. Aptamers are short strands of DNA.

Whilst the properties in terms of recognition for biological molecules are excellent, the performance and environmental stability is low and this can compromise their uses. In particular degradation is a major problem.

To combat these derogatory issues a new generation of artifical recognition materials have been developed. At the forefront is a technology called Molecular Imprinting. This involves making a small binding pocket in a polymer which is chemically and shape specific for the target compound. These "smart plastics" offer the robustness and the ability to work in extreme environmental conditions but can lack the needed specificity/affinity.

This project aims to create a "best of both worlds" scenario. By slightly changing the chemical structure of the aptamer DNA we intend to use the aptamer as the recognition part of a molecularly imprinted polymer (MIP). This will be achieved by making the aptamer polymerisable so it can become part of the polymer structure, incorporating it into the polymer matrix via polymerisable groups on the DNA.

In this way we intend to preserve the high affinity and specificity of the aptamer whilst imparting the robustness and added shape specificity generated by the MIP. The presence of the polymer should protect the aptamer from environmental degradation and potentially widen the scope of use of aptamers for recognition.

Planned Impact

Successful development of aptamer-MIP hybrid materials would pave the way for a new generation of molecularly imprinted polymers. By improving the recognition properties of this class of polymer it would pave the way for their use to become more mainstream, offering significant commercial gain.

The benefits to the aptamer community would be high as well. Currently uses of them are often limited by environmental considerations. Incorporation into a robust material whilst maintaining mode of action would be a benefit for several uses and this has clear commerical aspects.

The development of novel DNA chemistry, proposed in this paper opens up futher methods to interact DNA with other materials, especially materials considered to be "artificial". This marrying of biological and synthetic technology would be invaluable.

If successful this work will open up a new avenue of research, with will benefit the wide community and help position the PI as world leaders in novel recognition elements.

Additionally, any peer-reviewed publications arising from this grant will be registered on the Open University's open access institutional repository - Open Research Online (ORO) at http://oro.open.ac.uk. ORO is now one of the largest HEI repositories in the UK with over 850,000 visits from people in 170 countries since 2006. It enables access to research outputs via common search engines including Google, by using the OAI (Open Archives Initiative) Protocol for Metadata Harvesting.

Publications

10 25 50
 
Description The proposal was to study a new type of molecularly imprinted polymer using an aptamer (single strand DNA chain) as a recognition element for small molecules.
New polymeric materials were developed which allow for the incorporation of aptamers via the use of a polymerisable thymine base, into nanoparticles. Studies into suitable polymerisable bases were carried out.
Nanoparticles were developed for:
1: Base recognition (A-T) DOI: 10.1021/ma501530c
2: DNA sequence recognition (12 base pair recognition using complimentary strands)10.1039/C5BM00341E
3: Small molecule recognition (cocaine) DOI: 10.1002/adma.201404235
Exploitation Route The demonstration of this opens up a wide range of areas. A number of further studies into the particular chemistries exist including:
* exploring different chemistries for DNA (aptamer) attachment to polymers to expand potential flexibility of this technique.
* exploring the use of the MIP polymer scaffold as a protective device for aptamer technologies.
* exploring the possibility of DNA sequence recognition (longer sequences, sequence mismatch)
* incorporation of signal transduction onto nanoparticles.
* further development of materials for bioactive compounds for both sensing and drug delivery.
It is my intention to generate further applications to EPSRC within a collaborative network led by myself.

2017 : Further support for this work applied for to EPSRC.
Project continuing via Santander fund targeting small proteins
Sectors Agriculture, Food and Drink,Chemicals,Environment,Pharmaceuticals and Medical Biotechnology

 
Description To early to tell though early discussions are occurring with an Aptamer research company. The results have been published and are currently being used for support for further funding. 2017 : NDA's signed. Aptamer group supported in kind for EPSRC bid follow up. 2018: Follow up grant submitted. awaiting result. Small travel grant was successful to allow for further experimentation, currently under study. 2019: Grant (EP/S003339/1) was submitted and successful. 2021: This has led to a full collaboration where details are explained in the follow-on grant submission. There is an exploration of improving the companies materials and development of new avenues of research. To Date we are looking at developing novel materials for detection of antibiotics and viral proteins, especially targeting COVID. while these materials are still in early stages the potential for robust detection methods offer significant potential impacts. This grant led to this point and i will update further on the next grant.
First Year Of Impact 2014
Sector Agriculture, Food and Drink,Chemicals,Environment,Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Economic

 
Description Exploration of Linking Chemistry in the Design of Aptamer-Molecularly Imprinted Polymer Hybrids (aptaMIPs)
Amount £294,568 (GBP)
Funding ID EP/S003339/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 07/2019 
End 07/2021
 
Description Santander Resaerch Travel Award
Amount £4,800 (GBP)
Organisation Santander Bank 
Sector Private
Country United States
Start 03/2017 
End 07/2017
 
Description Apatmer Group 
Organisation Aptamer Group
Country United Kingdom 
Sector Private 
PI Contribution From the grant linked this has led to a new partnership in progress with The Aptamer group (York) for support of grant submission. This grant has provided an active collaboration and we are moving forward with discussions on further applications. We are working on development of hybrid materials using materials from the company. Several publications are in draft where we are improving aptamers through this method. A formal NDA/MTA is in place Aptamer group have supported with in-kind support a fellowship bid (EPSRC Dec 2020)
Collaborator Contribution AG are providing sequences for specific targets that we are using for basing the research on. Support for EPSRC Fellowship bid. (Dec 2020)
Impact Two publications are under review and should be published in April. Several further are in progress including COVID targeting.
Start Year 2015
 
Description DNA chemistry 
Organisation University of Massachusetts
Department RNA therapeutics institute
Country United States 
Sector Academic/University 
PI Contribution I have been leading this project (EP/K015095/1) but required a DNA chemist to help develop potential base chemistries. Using the synthesisied sequences prepared by Dr Watts' team I have generated and tested polymeric materials.
Collaborator Contribution With Dr Jon Watts I have built a collaboration supporting EP/K015095/1. Dr Watts have provided synthesis and base design work for the progress of this project. Support for EPSRC proposal follow up EP/P026559/1 (at panel 7th March)
Impact I have given a seminar at Southampton, and likewise Dr Watts has spoken here at the OU. There are 3 papers in publication, 1 published, 1 accepted and 1 under review on date of completion of this form. The joint work has been presented at a number of conferences. JW has moved from Southampton to UMass. Has supported further work by sample prep. Santander grant awarded for travel for further research
Start Year 2013
 
Description Nanoparticles 
Organisation University of Leicester
Country United Kingdom 
Sector Academic/University 
PI Contribution I have strong links with the research group of Professor Piletsky, recently of Cranfield, but now Leicester Chemistry. We have regular research meetings to discuss current projects and future ideas. We also share equipment and methods.
Collaborator Contribution Discussions on nanoparticle production and use of specialized equipment based at Leicester. Support on EPSRC submission (letter of support as project partner)
Impact Several papers as found in Publications
 
Description Supermonomer design - David Fulton 
Organisation Newcastle University
Department Institute of Cellular Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution Through the work started with this grant I have generated a working relationship with Dr David Fulton towards developing supermonomers for imprinting using dynamic combinatorial chemistry. This fledgling collaboration towards a Leverhulme bid (submission 1st Apr 2017) which was not successful. Based on this we have worked again, supported by the results of this grant, a further application to EPSRC responsive mode. Submitted October 2020
Collaborator Contribution Joint writing of proposals
Impact Grant submission (1st Apr 2017) GRant submission (2nd Oct 2020)
Start Year 2016
 
Description EPSRC (Inspire) meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Engaged with peers and field leaders in discussions on joint collaborative projects, and career trajectory.

Inspire bid submitted joint with Kent (Arnold), Durham (Beaumont), Liverpool (Cowan) and York (McKenna).
Two further delegates were invited for talks and further collaborative discussions at the OU, Moram (Imperial) and Karenowska (Oxford). The latter of which is still continuing.
I have also enaged in a collaborative study on electropolymers with Alexander Cowan (Liverpool)
Year(s) Of Engagement Activity 2014
 
Description EPSRC - building tomorrows leaders 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Invited EPSRC workshop
Year(s) Of Engagement Activity 2015
 
Description EPSRC prioristation panel member 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact EPSCRC chemistry panel member December 2015
Year(s) Of Engagement Activity 2015
 
Description Invited Talk (Verona) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Seminar at University of Verona
Year(s) Of Engagement Activity 2017
 
Description Lecture Tour (New Zealand) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Funds acquired from NERC CENTA travel scheme to visit New Zealand to give a series of lectures.Lectures at: Auckland University, Waikato University, SCION and Blenheim High School.
Year(s) Of Engagement Activity 2017
 
Description Lecture Tour (USA) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Working from the Santander grant i visited University of Massachusetts and gave a series of talks in both research and education.
Year(s) Of Engagement Activity 2017
 
Description SCI conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Talk and Poster given by Dr Poma (PDRA)


Awarded 1st prize in the poster section.
Year(s) Of Engagement Activity 2013
URL http://www.soci.org/Chemistry-and-Industry/Academic-Posters/2013/SCI-Members-Forum-2013/Generation-o...
 
Description Smart Materials 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Through this work i have created a new cross departmental research group which has presented our research at the MRE2018.
Year(s) Of Engagement Activity 2018
URL http://www.mre2018.co.uk/
 
Description Talk (Birmingham) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact Academic talk (Birmingham university)
Year(s) Of Engagement Activity 2015
 
Description Talk (Durham) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Academic invited talk
Year(s) Of Engagement Activity 2016
 
Description Talk (Kent) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Presented work based on current grant - led to discussions and interest in MIP technique

invitation to join a potential collaboration for EPSRC bid (in preparation)
Year(s) Of Engagement Activity 2014
 
Description Talk (Southampton) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Talk to collaborator and other academics
Given that this was my first university a number of academics who taught me were present which has led to interest in my work.

Supported current collaboration with Dr Watts and identified potential further collaboration options.
Year(s) Of Engagement Activity 2014
 
Description Talk (Sydney, Australia) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Research talk to demonstrate the scope of imprinting technologies

In talks for potential collaborations and student enquiry interest in visiting my lab
Year(s) Of Engagement Activity 2014
 
Description Talk (University of Newcastle, Australia) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact A lot of interest in the new imprinting methods I am using, from the main groups there.

opportunity to return on sabbatical offered
Year(s) Of Engagement Activity 2014