Research Projects

Acid-degradable polymers for nonviral gene delivery

acid The development of a safe and efficient nonviral gene delivery system remains the greatest hurdle towards its application in gene therapy. BioTEL develops a variety of acid-degradable polymers that can facilitate endosomal escape and intracellular release of nucleic acids (e.g., plasmid DNA or siRNA) at the desired intracellular targets. Concurrently, the physicochemical properties and gene delivery efficiencies of the polyplexes formed by the polymers and nucleic acids is investigated to understand the fundamental relationship between polymer structure and biological activity. Lastly, hybrid polymeric nanoparticles as stimuli-responsive nanotheragnostic agents for use in combined imaging and therapy is also being developed.

Virus-mimicking core-shell nanoparticles for versatile gene therapy

virusGene therapy holds great promise for treating a number of diseases caused by genetic abnormalities. However, developing safe and efficient gene delivery vectors is still a major challenge. Widely used viral vectors are highly efficient but suffer significant drawbacks such as immunogenicity and innately limited cargo capacity. Non-viral vectors, though far less efficient than viral vectors, provide large cargo loading capacity, flexible modifications for versatile applications, and low immunogenicity. Therefore, developing safe and efficient non-viral vectors that mimic the cell-infecting mechanisms of viral vectors is of great interest.  in BioTEL, we are interested in developing non-viral core-shell nanoparticles that encapsulates the gene cargo in the core with a stimuli-responsive (e.g. acid-degradable via ketal linkage) polymeric shell synthetically mimicking the structure and infection mechanism of viral vectors.

Bioorthogonally modified retroviruses

BioorthogonallyRetroviruses are key vectors in clinical gene therapy because of their ability to achieve sustained transgene expression with relatively low immunogenicity. Introduction of specific functional molecules onto retroviral surfaces (envelope) to enable ease of purification, labeling, and targeted transduction is highly desired. A project in BioTEL involves developing a novel, efficient, and convenient method of functionalizing retroviral surfaces by applying bioorthogonal chemistry at both viral and cellular levels for direct and indirect modifications. This method of molecularly tuning retroviral surface at both viral and cellular levels offers wide potential applications and convenient preparation, which addresses important technical obstacles in utilizing retroviruses as key therapeutics for gene delivery.

Stimuli-responsive optical imaging contrast agent

stimuliGold nanoparticles (Au NPs) have been broadly used as biomedical sensors because Au NPs are biocompatible, easy to synthesize and exhibit unique physical properties including surface plasmon resonance effect (SPR). SPR of Au NPs strongly depends on particle size, shape and structure. In BioTEL, we collaborate with the Beckman Laser Institute to develop Au NPs as contrast agents for optical coherence tomography (OCT). OCT non-invasively detects scattering signals of samples and can be used to diagnose cancer producing high resolution tomography images in real time. However, detection of early stage of cancer requires enhancing/improving OCT contrast.  We seek to combine the tunable properties of Au NPs with stimuli response therapeutic packaging modalities to address the current OCT limitations.

DNA-based cancer vaccine

Gene therapy is a widely explored option as a potential and promising treatment for cancer.  Among the many different approaches, DNA-based vaccines have gained much attention in recent years.  BioTEL seeks to utilize a proprietary non-viral core-shell carrier system that safely and efficiently delivers the genes of interest into target cells.  Additionally, these carrier systems will be modified with therapeutic agents to simultaneously enhance the overall gene delivery and expression processes.  The emphasis of this project is to employ our DNA vaccines to prime specific antigen presenting cells in order to condition the body’s immune system against cancer.