On August 10, 2018 the US Food and Drug Administration (FDA) approved ONPATTRO™, a
nanomedicine for treating the devastating and usually lethal hereditary disease known as
hereditary transthyretin-induced amyloidosis (hATTR). The approval of ONPATTRO™ has
opened the door to a new era of gene therapies to treat most human diseases—including
genetic disorders, infections, chronic diseases and cancer—more effectively.
“It is just a matter of time.” This is the implication of a commentary published today in Nature
Nanotechnology by the scientists and pharmaceutical experts behind the development of
The senior author of the commentary is Dr. Pieter Cullis, former Director of the Life Sciences
Institute, and Professor of Biochemistry and Molecular Biology at the University of British
Columbia (UBC), whose laboratory contributed to the revolutionary lipid nanoparticle (LNP) delivery
technology behind ONPATTRO’s success.
ONPATTRO™ consists of LNPs containing short interfering RNA (siRNA) that, when delivered
to the interior of a target cell, “silences” the gene that codes for mutated transthyretin (TTR) and
thus prevents formation of the amyloid plaques characteristic of hATTR. ONPATTRO™ is the
first RNA interference (RNAi) drug ever approved by the FDA. This ushers in an entirely new
class of gene therapy medicines that have the potential to treat most diseases by silencing
proteins causing disease or producing proteins to treat disease.
“These results validate work we have conducted for more than 20 years to develop LNP
delivery systems that facilitate intracellular delivery of RNA and DNA polymers,” comments
Dr. Cullis, who is also the Scientific Director and CEO of the recently launched NanoMedicines
Innovation Network (NMIN), a Canadian Networks of Centre of Excellence.
“ONPATTRO builds on experience gained developing LNP delivery systems in my laboratory at
UBC since I established it in 1978. In many ways the success of ONPATTRO™ is the highpoint
of my career — at least, so far.”
“So far” because, as Dr. Cullis and colleagues explain in their commentary this is only the
beginning of a new era of medicine enabled by nanotechnology.
“The major advance embodied by ONPATTRO™ is the ability to deliver large nucleic acid
polymers into the interior of target cells” note the authors. More recent work has shown that
related LNP systems can effectively deliver much larger messenger RNA (mRNA)
molecules to produce or “express” therapeutic proteins.
“LNP systems containing mRNA can utilize the liver as a bioreactor producing therapeutic
proteins to fight disease,” comments co-author Dr. Dominik Witzigmann, a post-doctoral
fellow in Dr. Cullis’ lab and the administrative lead for NMIN’s NanoCore, a facility offering
services to assist with the clinical translation of nanomedicines.
“These systems are showing promise as highly effective vaccines for infectious diseases
such as the Zika or influenza virus. LNPs containing mRNA coding for programmable
nucleases, on the other hand, show considerable potential for gene editing directly within
Challenges remain, the authors acknowledge. However, they add that “the rapid advances of
recent years suggest that it is just a matter of time before these challenges are overcome.”
The story of ONPATTRO™, detailed in the Nature Nano commentary, illustrates how
nanomedicines are increasingly positioned to become the next generation of pharmaceuticals
by enabling large molecules such as nucleic acid-based drugs, to be used therapeutically.
These gene medicines will dramatically expand the range of diseases that can be treated in a
precise and effective manner.
The NanoMedicines Innovation Network (NMIN) is a national research network dedicated to
advancing research, innovation & training in nanomedicines to maintain Canada as the world
leader in this revolutionary approach to treat & cure disease. Funded by the Government of
Canada through the federal Networks of Centres of Excellence (NCE) Program, the Network is
hosted at the University of British Columbia in Vancouver, British Columbia.
From a press release published by NMIN Dec 4, 2019