Pieter Cullis

Pieter Cullis (born May 12, 1946, Barnard Castle, England) is a Canadian biochemist and physicist who made groundbreaking contributions to the field of lipid chemistry, particularly in his work with lipid bilayers and the encapsulation of drugs and nucleic acids. His foundational research on lipid nanoparticles (LNPs) revolutionized drug delivery, notably enabling advances in the development of mRNA vaccines, gene therapies, and targeted cancer treatments. Cullis’s work was central to the development of the Pfizer-BioNTech COVID-19 vaccine in 2020.

Early life and education

When Cullis was eight, his family moved from England to West Vancouver, British Columbia, Canada, where he later attended West Vancouver High School. Inspired by his father, who taught physics, he developed an interest in the field and went on to earn bachelor’s (1967) and doctoral (1972) degrees in physics from the University of British Columbia (UBC). His early academic pursuits focused on basic physical principles, but during his postdoctoral studies at the University of Oxford and Utrecht University he pivoted toward biochemistry. In 1978 he returned to UBC, where he joined the department of biochemistry and molecular biology, serving as assistant professor and, from 1985, full professor. From 2013 to 2017 he was the director of UBC’s Life Sciences Institute.

Advances in LNP technology

At UBC, Cullis established a research career focused on fundamental lipid chemistry and translational nanomedicine, in which nanotechnology-based innovations are advanced from the laboratory into clinical medicine. In the late 1970s his studies of lipid membrane behavior using model systems gave new insight into lipid diversity and asymmetry. To facilitate his research, he invented an LNP extruder device, which accelerated the production of LNPs. Other researchers were soon interested in the device, leading Cullis and his collaborator Michael Hope to form Lipex Biomembranes to support its production and sale.

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Through the 1980s Cullis pioneered methods to load anticancer drugs into LNPs. In particular, he contributed to the development of techniques for gradient-based drug loading for liposomal formulations, which allowed for significantly greater drug encapsulation compared with passive methods. These approaches ultimately fueled the development of several cancer treatments, including Myocet (doxorubicin hydrochloride; first approved in Europe in 2000) and Vyxeos (daunorubicin and cytarabine; approved in the United States in 2017). Cullis continued to investigate strategies to improve the effectiveness and safety of LNP-based therapeutics with Inex Pharmaceuticals and its spin-off, Protiva Biotherapeutics.

RNA-based LNPs

By the early 2000s Cullis and his team were again advancing the use of LNPs, this time for the encapsulation of nucleic acids for applications in gene therapy. In 2005, working with Massachusetts-based Alnylam Pharmaceuticals, Inc., he and colleagues developed LNP technology to deliver RNA-based drugs to cells. This work leveraged RNA interference (RNAi) technology, specifically using short interfering RNA (siRNA), to silence the activity of a gene called transthyretin (TTR). Mutations in this gene cause hereditary TTR amyloidosis (hATTR), a progressive life-threatening disease. The siRNA drug patisiran (marketed as Onpattro) was approved by the U.S. Food and Drug Administration in 2018 for the treatment of polyneuropathy (nerve damage) associated with hATTR.

In 2009 Cullis cofounded Acuitas Therapeutics, which focused on the advancement of LNP drug delivery systems for messenger RNA (mRNA) and vaccines. Initially, Cullis worked with immunologists Drew Weissman and Katalin Karikó, who wanted to utilize LNPs for a novel vaccine for Zika fever. Having achieved success in small animal and primate studies, Acuitas then partnered with BioNTech, where Karikó was senior vice president. The companies began collaborating to develop LNPs for the delivery of mRNA-based cancer drugs, as well as an influenza vaccine. In 2020, when the COVID‑19 pandemic emerged, Acuitas licensed its mRNA LNP technology to BioNTech, which, in collaboration with the pharmaceutical manufacturer Pfizer, quickly generated an mRNA vaccine that could help prevent or reduce the severity of infection with SARS-CoV-2, the virus that causes COVID-19.

Later career

Following the success of the COVID-19 vaccine, Cullis continued to focus on refining LNP technology to improve the delivery of siRNA, mRNA, and various types of drugs. At UBC his team developed new classes of ionizable cationic (positively charged) lipids that enhance circulation stability and improve endosomal release, making nucleic acid therapies more precise and effective. Through NanoVation Therapeutics, which he cofounded in 2020, Cullis worked to translate these innovations into next-generation nanomedicines. He also led Canada’s NanoMedicines Innovation Network (NMIN) until 2024, when it fulfilled its mandates set forth by Canada’s Networks of Centres of Excellence; Cullis had founded NMIN in 2019 to inspire a national platform for vaccine and therapeutic development.

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Awards and other honors

Cullis has been recognized with numerous accolades for his work. Notable among them were the Prince Mahidol Award (2021), VinFuture Grand Prize (2021), Canada Gairdner International Award (2022), and Tang Prize (2022). He was appointed an Officer of the Order of Canada in 2021 and became a fellow of the Royal Society in 2023. The following year he was inducted into the Canadian Medical Hall of Fame.