Cullis's research interests concern the roles of lipids in biological membranes and the development of nanomedicines using lipid nanoparticle (LNP) technology. His studies on the roles of lipids focus on two areas. The first concerns the ability of membrane lipids to adopt non-bilayer structures and the roles of such structures in processes such as membrane fusion. The second area focuses on transport across bilayer lipid systems induced by trans-bilayer ion gradients. His interests in nanomedicines first concern the design and synthesis of LNP delivery systems containing small molecule drugs, particularly drugs used in cancer chemotherapy, with the aim of increasing potency and reducing toxicity by enhancing drug delivery to, and release at, sites of disease such as tumours. A second area involves using LNP technology to enable the therapeutic use of macromolecular genetic drugs such as small interfering RNA (siRNA) and messenger RNA (mRNA) for gene therapy, including gene editing. These efforts have led to five nanomedicines that have been approved for clinical use by regulatory agencies such as the US Food and Drug Agency (FDA), the European Medicines Agency and Health Canada (see Table below).

Two of these nanomedicines were recently approved and are of particular note. First is the drug Onpattro, a gene therapy that was approved (August 2018) by the FDA to treat hereditary amyloid transthyretin (hATTR) amyloidosis. Onpattro is the first-in-class RNAi-based drug to be approved by the FDA and employs an LNP delivery system developed in collaboration with Alnylam Pharmaceuticals (Boston), his laboratory at UBC and two spin-offs that he co-founded (Protiva/Arbutus and Acuitas Therapeutics). Onpattro delivers an siRNA to silence the TTR gene in the liver. A remarkable feature of Onpattro is that it is able to not only stop further progression of this hitherto untreatable disease (which usually leads to death within five years of diagnosis), but also to reverse the neuropathies and cardiovascular issues associated with hATTR. The second class of medicines are the mRNA Covid 19 vaccines that Acuitas developed with Pfizer/BioNTech and CureVac. The Pfizer/BioNTech COVID-19 mRNA vaccine BNT162b2 relies on an LNP delivery system developed by Acuitas. BNT162b2 (Comirnaty) was approved for emergency use^[2] (December 2020) by the US FDA and has subsequently been approved by the US^[3], UK, Canada, Europe and many other countries worldwide. These approvals were made on the basis of a 95% efficacy in preventing COVID-19, together with an excellent safety profile. More than five billion doses of this vaccine were administered globally in 2021-22 and the vaccine has been credited with saving over six million lives in 2021 alone^[4].

The following approved nanomedicine drugs have been co-developed by Cullis's laboratory at the University of British Columbia and by the companies he has co-founded (Inex Pharmaceuticals Corp, Protiva Biotherapeutics, Canadian Liposome Company, Acuitas Therapeutics).