Lessons learned from the SARS-CoV-2 pandemic; from nucleic acid nanomedicines, to clinical trials, herd immunity, and the vaccination divide.

INTRODUCTION: In November 2019, the idea of a zoonotic virus crossing over to human transmission in a seafood market in Wuhan, China, and then soaring across the globe to claim over 6.3 million lives and persisting to date, seemed more like wild science fiction than a future reality. As the SARS-CoV-2 pandemic continues, it is important to hallmark the imprints the pandemic has made on science. AREAS COVERED: This review covers the biology of SARS-CoV-2, vaccine formulations and trials, the concept of 'herd resistance,' and the vaccination divide. EXPERT OPINION: The SARS-CoV-2 pandemic has changed the landscape of medicine. The rapid approval of SARS-CoV-2 vaccines has changed the culture of drug development and clinical approvals. This change is already leading to more accelerated trials. The RNA vaccines have opened the market for nucleic acid therapies and the applications are limitless - from cancer to influenza. A phenomenon that has occurred is that the low efficacy of current vaccines and the rapid mutation rate of the virus is preventing herd immunity from being attained. Instead, herd resistance is being acquired. Even with future, more effective vaccines, anti-vaccination attitudes will continue to challenge the quest for SARS-CoV-2 herd immunity.

Mitochondrial nanomedicine: Subcellular organelle-specific delivery of molecular medicines.

As mitochondria network together to act as the master sensors and effectors of apoptosis, ATP production, reactive oxygen species management, mitophagy/autophagy, and homeostasis; this organelle is an ideal target for pharmaceutical manipulation. Mitochondrial dysfunction contributes to many diseases, for example, ß-amyloid has been shown to interfere with mitochondrial protein import and induce apoptosis in Alzheimer's Disease while some forms of Parkinson's Disease are associated with dysfunctional mitochondrial PINK1 and Parkin proteins. Mitochondrial medicine has applications in the treatment of an array of pathologies from cancer to cardiovascular disease. A challenge of mitochondrial medicine is directing therapies to a subcellular target. Nanotechnology based approaches combined with mitochondrial targeting strategies can greatly improve the clinical translation and effectiveness of mitochondrial medicine. This review discusses mitochondrial drug delivery approaches and applications of mitochondrial nanomedicines. Nanomedicine approaches have the potential to drive the success of mitochondrial therapies into the clinic.

Clinical approval of nanotechnology-based SARS-CoV-2 mRNA vaccines: impact on translational nanomedicine.

One year after the first human case of SARS-CoV-2, two nanomedicine-based mRNA vaccines have been fast-tracked, developed, and have received emergency use authorization throughout the globe with more vaccine approvals on the heels of these first two. Several SARS-CoV-2 vaccine compositions use nanotechnology-enabled formulations. A silver lining of the COVID-19 pandemic is that the fast-tracked vaccine development for SARS-CoV-2 has advanced the clinical translation pathway for nanomedicine drug delivery systems. The laboratory science of lipid-based nanoparticles was ready and rose to the clinical challenge of rapid vaccine development. The successful development and fast tracking of SARS-CoV-2 nanomedicine vaccines has exciting implications for the future of nanotechnology-enabled drug and gene delivery; it demonstrates that nanomedicine is necessary and critical to the successful delivery of advanced molecular therapeutics such as nucleic acids, it is establishing the precedent of safety and the population effect of phase four clinical trials, and it is laying the foundation for the clinical translation of more complex, non-lipid nanomedicines. The development, fast-tracking, and approval of SARS-CoV-2 nanotechnology-based vaccines has transformed the seemingly daunting challenges for clinically translating nanomedicines into measurable hurdles that can be overcome. Due to the tremendous scientific achievements that have occurred in response to the COVID-19 pandemic, years, perhaps even decades, have been streamlined for certain translational nanomedicines.