Documentary “NNI Retrospective Video: Creating a National Initiative” celebrates the US National Nanotechnology Initiative (NNI) and a lipid nanoparticle question

i stumbled across an August 4, 2022 news release about a video celbrating the US National Nanotechnology Initiative’s (NNI) over 20 years of operation, (Note: A link has been removed),

TV Worldwide, since 1999, a pioneering web-based global TV network, announced that it was releasing a video trailer highlighting a previously released documentary on NNI over the past 20 years, entitled, ‘NNI Retrospective Video: Creating a National Initiative’.

The video and its trailer were produced in cooperation with the National Nanotechnology Initiative (NNI), the National Science Foundation and the University of North Carolina Greensboro.

Video Documentary Synopsis

Nanotechnology is a megatrend in science and technology at the beginning of the 21 Century. The National Nanotechnology Initiative (NNI) has played a key role in advancing the field after it was announced by President Clinton in January 2000. Neil Lane was Presidential Science Advisor. Mike Roco proposed the initiative at the White House in March 1999 on behalf of the Interagency Working Group on Nanotechnology and was named the founding Chair of NSET to implement NNI beginning with Oct. 2000. NSF led the preparation of this initiative together with other agencies including NIH, DoD, DOE, NASA, and EPA. Jim Murday was named the first Director of NNCO to support NSET. The scientific and societal success of NNI has been recognized in the professional communities, National Academies, PCAST, and Congress. Nanoscale science, engineering and technology are strongly connected and collectively called Nanotechnology.

This video documentary was made after the 20th NNI grantees conference at NSF. It is focused on creating and implementing NNI, through video interviews. The interviews focused on three questions: (a) Motivation and how NNI started; (b) The process and reason for the success in creating NNI; (c) Outcomes of NNI after 20 years, and how the initial vision has been realized.

About the National Nanotechnology Initiative (NNI)

The National Nanotechnology Initiative (NNI) is a U.S. Government research and development (R&D) initiative. Over thirty Federal departments, independent agencies, and commissions work together toward the shared vision of a future in which the ability to understand and control matter at the nanoscale leads to ongoing revolutions in technology and industry that benefit society. The NNI enhances interagency coordination of nanotechnology R&D, supports a shared infrastructure, enables leveraging of resources while avoiding duplication, and establishes shared goals, priorities, and strategies that complement agency-specific missions and activities.

The NNI participating agencies work together to advance discovery and innovation across the nanotechnology R&D enterprise. The NNI portfolio encompasses efforts along the entire technology development pathway, from early-stage fundamental science through applications-driven activities. Nanoscience and nanotechnology are prevalent across the R&D landscape, with an ever-growing list of applications that includes nanomedicine, nanoelectronics, water treatment, precision agriculture, transportation, and energy generation and storage. The NNI brings together representatives from multiple agencies to leverage knowledge and resources and to collaborate with academia and the private sector, as appropriate, to promote technology transfer and facilitate commercialization. The breadth of NNI-supported infrastructure enables not only the nanotechnology community but also researchers from related disciplines.

In addition to R&D efforts, the NNI is helping to build the nanotechnology workforce of the future, with focused efforts from K–12 through postgraduate research training. The responsible development of nanotechnology has been an integral pillar of the NNI since its inception, and the initiative proactively considers potential implications and technology applications at the same time. Collectively, these activities ensure that the United States remains not only the place where nanoscience discoveries are made, but also where these discoveries are translated and manufactured into products to benefit society.

I’m embedding the trailer here and a lipid nanoparticle question follows (The origin story told in Vancouver [Canada] is that the work was started at the University of British Columbia by Pieter Quilty.),

I was curious about what involvement the US NNI had with the development of lipid nanoparticles (LNPs) and found a possible answer to that question on Wikipedia The LNP Wikipedia entry certainly gives the bulk of the credit to Quilty but there was work done prior to his involvement (Note: Links have been removed),

A significant obstacle to using LNPs as a delivery vehicle for nucleic acids is that in nature, lipids and nucleic acids both carry a negative electric charge—meaning they do not easily mix with each other.[19] While working at Syntex in the mid-1980s,[20] Philip Felgner [emphasis mine] pioneered the use of artificially-created cationic lipids (positively-charged lipids) to bind lipids to nucleic acids in order to transfect the latter into cells.[21] However, by the late 1990s, it was known from in vitro experiments that this use of cationic lipids had undesired side effects on cell membranes.[22]

During the late 1990s and 2000s, Pieter Cullis of the University of British Columbia [emphasis mine] developed ionizable cationic lipids which are “positively charged at an acidic pH but neutral in the blood.”[8] Cullis also led the development of a technique involving careful adjustments to pH during the process of mixing ingredients in order to create LNPs which could safely pass through the cell membranes of living organisms.[19][23] As of 2021, the current understanding of LNPs formulated with such ionizable cationic lipids is that they enter cells through receptor-mediated endocytosis and end up inside endosomes.[8] The acidity inside the endosomes causes LNPs’ ionizable cationic lipids to acquire a positive charge, and this is thought to allow LNPs to escape from endosomes and release their RNA payloads.[8]

From 2005 into the early 2010s, LNPs were investigated as a drug delivery system for small interfering RNA (siRNA) drugs.[8] In 2009, Cullis co-founded a company called Acuitas Therapeutics to commercialize his LNP research [emphasis mine]; Acuitas worked on developing LNPs for Alnylam Pharmaceuticals’s siRNA drugs.[24] In 2018, the FDA approved Alnylam’s siRNA drug Onpattro (patisiran), the first drug to use LNPs as the drug delivery system.[3][8]

By that point in time, siRNA drug developers like Alnylam were already looking at other options for future drugs like chemical conjugate systems, but during the 2010s, the earlier research into using LNPs for siRNA became a foundation for new research into using LNPs for mRNA.[8] Lipids intended for short siRNA strands did not work well for much longer mRNA strands, which led to extensive research during the mid-2010s into the creation of novel ionizable cationic lipids appropriate for mRNA.[8] As of late 2020, several mRNA vaccines for SARS-CoV-2 use LNPs as their drug delivery system, including both the Moderna COVID-19 vaccine and the Pfizer–BioNTech COVID-19 vaccines.[3] Moderna uses its own proprietary ionizable cationic lipid called SM-102, while Pfizer and BioNTech licensed an ionizable cationic lipid called ALC-0315 from Acuitas.[8] [emphases mine]

You can find out more about Philip Felgner here on his University of California at Irvine (UCI) profile page.

I wish they had been a little more careful about some of the claims that Thomas Kalil made about lipid nanoparticles in both the trailer and video but, getting back to the trailer (approx. 3 mins.) and the full video (approx. 25 mins.), either provides insight into a quite extraordinary effort.

Bravo to the US NNI!

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