Idris Raji

Research Description

The Raji laboratory is interested developing nanoparticle-based delivery systems to support early-stage translation of genetic medicines and vaccines. We are particularly interested developing deformable nanoparticles that will facilitate in-vivo delivery of genetic medicines and vaccines to diseased tissues. Our interest in this is fueled by our desire to understand the intricacies of the interactions between nanoparticles and protein coronas that influence their tissue distribution. We are also actively involved in developing small molecule-based therapeutics that harness the power of the immune system to instigate disease-specific immune responses.  

Nanoparticles for genetic medicines and vaccines

Lipid nanoparticle (LNP) is the most clinically advanced biomaterial for nucleic acid delivery, but its use is currently limited to mRNA vaccine. The use of LNP for non-vaccine applications has been hampered by their lack of tissue specificity and toxicity. Also, a one-size-fits-all approach does not work for LNP design, which means LNP for specific applications must be developed from scratch. Additionally, there is a gap in our understanding of what drives LNP to localize in different tissues. Our lab is deploying novel chemical reactions to facilitate rapid synthesis and screening of thousands of LNP to identify safe and efficient LNP for in-vivo delivery of genetic medicines to hepatic and non-hepatic tissues. Also from our screen, we hope to understand how interactions of LNP with different protein coronas drive their tissue localization.

Small molecule immune modulators

The immune system presents a plethora of opportunities to develop therapeutics for different diseases. We are interested in developing molecules that modulate the functions of proteins relevant in immune activation. One of such is Stimulator of Interferon Genes (STING), which is a key player in the mechanism of immune sensing of foreign nucleic acids and pathogens. Existing STING agonists have made little progress through clinical trials due to concerns over potency and toxicity. Using structure-guided drug design, fragment-based drug discovery and high-throughput virtual screening, our is developing potent and safe small molecule STING agonists taking cues from structural moieties found in biomaterials endowed with STING activating capability.

Molecular probes for studying epigenetic regulation of immune response

still within the context of harnessing the immune system for immunotherapeutic opportunities, our lab is interested in unraveling how epigenetic regulation influences innate immune response to diseases.  We are developing molecular scaffolds that perturb epigenetic modifying proteins and other proteins relevant in immune response, to understand the underlying mechanism of how epigenetic processes such as DNA methylation/demethylation, histone methylation/demethylation, histone acetylation/deacetylation etc. affect innate immune response to cancer and other infectious diseases.