Laboratories, Pharmacology / 25.05.2026
LNP technology in drug delivery – how lipid nanoparticles became the backbone of modern RNA therapeutics
For most of the history of RNA research, the molecule's therapeutic promise was undermined by a fundamental problem: RNA is unstable, immunogenic, and unable to cross cell membranes on its own. You could design a sequence that encoded exactly the right protein, synthesise it cleanly — and watch it degrade before reaching its target. The biology was understood; the delivery was the bottleneck.
Lipid nanoparticles solved that problem. Not all at once, and not simply — but the arc of LNP development over six decades produced the delivery technology that made RNA therapeutics clinically viable. The mRNA vaccines of 2020–2021 were the most visible expression of that achievement. They were not, however, the end of the story. They were the proof of concept that opened the pipeline.
Dr. Angélica Cifuentes Kottkamp[/caption]
Angélica
Dr. Dickerman[/caption]
Dr. Barbra Dickerman, PhD
CAUSALab investigator and instructor
Department of Epidemiology
Harvard T.H. Chan School of Public Health
MedicalResearch.com: What is the background for this study?
Response: Early randomized trials showed that the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines were both remarkably effective at preventing symptomatic disease, when comparing each vaccine with no vaccine. However, head-to-head comparisons of these vaccines have been lacking, leaving open the question of which vaccine is more effective.
In this study, we analyzed the VA’s high-quality databases in a way that emulated the design of the hypothetical trial that would have answered this question. Specifically, we used the findings from the original trials to benchmark our methods and then extended them to provide novel evidence for the comparative effectiveness of these two vaccines in a real-world setting and across diverse subgroups and different time periods.
Dr. Israel[/caption]
Ariel Israel, M.D., Ph.D.
Director, Leumit Health Services
Tel Aviv, Israel
MedicalResearch.com: What is the background for this study?
Response: As a research institute of Leumit, one of the four state mandated health funds in Israel, we pursue research projects aimed at improving the health of our members, and reducing the burden of disease. For this purpose, we harness the unique resource of the electronic health records of our members, that is available in a central data warehouse for research purposes.
Israel was one of the first countries to roll-out a large-scale vaccination campaign, and to achieve control of the pandemics through vaccination. Nevertheless, since the middle of June '21, we have observed a gradual increase in the rate of COVID-19 infections among our members, even among the vaccinated. This increase was first believed to be due to the emergence of the delta strain, but when we compared vaccinated individuals who suffered from breakthrough infections to other vaccinated individuals, we found that the time that has elapsed since vaccination was significantly longer for individuals who got infected with COVID-19, in each of the age groups.
This prompted us to investigate the issue of a possible waning effect of the vaccine protection with time, that we present in this report, using the test negative study design.
We examined the electronic health records for 80,057 adults (average age 44 years) who received a PCR test at least three weeks after their second injection, and had no evidence of previous covid-19 infection. Of these 80,057 participants, 7,973 (9.6%) had a positive test result. These individuals were then matched to negative controls of the same age and ethnic group who were tested in the same week.
Dr. Elwy[/caption]
Rani Elwy, PhD
Bridge Quality Enhancement Research Initiative Program, Center for Healthcare Organization and Implementation Research,
VA Bedford Healthcare System
Bedford, Massachusetts
Department of Psychiatry and Human Behavior, Alpert Medical School
Brown University, Providence, Rhode Island
MedicalResearch.com: What is the background for this study?
Response: The VA operates a very robust, embedded quality improvement and implementation science program, of which our team is involved. As the VA was one of the first US healthcare systems to rollout COVID-19 vaccination programs, we were asked to evaluate these efforts in real-time, to provide input to VA healthcare leaders on what was going well and what could be improved. This survey reported in JAMA Network Open is one of the quality improvement efforts we engaged in.
Dr. Blankson[/caption]
Joel N. Blankson, MD, PhD
Department of Infectious Diseases
Associate Professor
Cellular and Molecular Medicine Program
Johns Hopkins
MedicalResearch.com: What is the background for this study? Which vaccines did you evaluate?
Response: Prior studies from several groups including our own have found T cell cross-recognition of peptides from SARS-CoV-2 and the common cold coronaviruses.
We asked whether as a result of this cross-reactivity, immunization with the SARS-CoV-2 vaccine would also enhance T cell responses to the common cold coronaviruses.
Prior studies also suggested that antibodies elicited from the mRNA vaccines had a reduced ability to neutralize the emerging variants of concern.
Most of the study participants had received the Pfizer vaccine, but a few had received the Moderna vaccine. 
Dr. Meyer, J.D.[/caption]
Michelle N. Meyer, PhD, JD
Assistant Professor & Associate Director, Research Ethics, Center for Translational Bioethics & Health Care Policy
Faculty Co-Director, Behavioral Insights Team, Steele Institute for Health Innovation
Assistant Professor of Bioethics
Geisinger Commonwealth School of Medicine
Geisinger, PA
MedicalResearch.com: What is the background for this study?
Response: Earlier research had found people are less likely to say they'll receive a COVID-19 vaccine offered to them under an Emergency Use Authorization (EUA) than one offered to them following full FDA approval. Earlier surveys had also found that only around 30% of health care workers intended to receive a COVID-19 vaccine. Because the public often looks to local health care workers for health advice, and in most prioritization schemes they were slated to be offered vaccines first, this was quite concerning for the prospect of achieving population immunity. Commenters had warned that if the FDA chose to make COVID-19 vaccines available under EUAs, that substantial efforts would need to be made to ensure trust. On Dec. 4, 2020, an announcement about anticipated vaccine availability was emailed to all 23,784 Geisinger employees, who were asked to indicate their intention to receive a vaccine when one was available to them and the reasons for any hesitation they might have.
