Targeted Molecularly Imprinted Lipid Nanoparticles (MI-LNPs) for gene delivery

Project ID: 2228cd1351 (You will need this ID for your application)

UCL Lead department: Eastman Dental Institute

Project Summary:

Therapeutic nucleic acids are emerging as a new class of medicines which enable treatment of classically undruggable diseases by modulating the expression of therapeutic or disease related proteins. However, the fragility and poor cellular association of nucleic acids mean they require a delivery vector to protect the cargo and facilitate translocation across the cellular membrane. Lipid nanoparticles (LNPs) have now been clinically used for the mRNA vaccines against COVID-19 and therefore are among the most popular delivery system. It is critical administered LNPs are retained at the correct tissues and cells, however there is no route to retarget LNPs without altering their base composition.

To address this major drawback, the main aim of this project is to develop a LNP system which exploits molecular imprinting technology. Molecular imprinting describes the creation of artificial molecular recognition sites in a functional synthetic polymer by the process of forming a polymer in the presence of a “template”, i.e. the target of interest. Molecularly imprinted polymers (MIPs) therefore act as synthetic antibodies with high binding affinity for their target. This project will assess whether such molecular imprinting technology can be integrated within LNPs surface to target and deliver nucleic acids to specific cells (e.g., salivary glands, or heart).

There are three main objectives for this research project:

Development of Molecularly Imprinted LNPs (MI-LNPs) for the desired targets via solid-phase synthesis.
Physico-chemical characterisation and formulation robustness assessment MI-LNPs.
In vitro and potential and potential in vivo characterisation of MI-LNPs