Using Lipid Nanoparticles (LNPs) for mRNA Delivery

With all the setbacks and frustrations of the COVID-19 pandemic, one positive development was the production of several vaccines using mRNA (Messenger Ribonucleic Acid) technology.

mRNA vaccines

Unlike traditional vaccines which inject a weakened or inactive virus into the body, mRNA vaccines use mRNA, an important component of all cells. Messenger RNA is a key to protein synthesis and gene expression; whereas RNA converts genetic information from DNA, mRNA copies the genetic blueprint and carries it over for protein production. Thus, mRNA is the key molecule to enable protein synthesis, such as the production of antigens.

mRNA vaccines work by utilizing these harmless antigens, introduced to the body by the vaccine, to trigger a natural immune response and produce specific antibodies against the virus.

Although new to the general population, mRNA technology had been studied for decades in an effort to provide cures to many diseases which had been plaguing the world for years. However, when the COVID-19 pandemic hit, the scientific community shifted gears and collectively searched for and developed new vaccines at record speed.

Aided by not only mRNA technology but virtually unlimited global financial resources, government support and unified, global talent, viable mRNA vaccines were not only achieved in record time but were also able to meet the rigorous standards of the United States Food and Drug Administration (FDA) and achieve full approval.¹

What's next for mRNA technology?

With mRNA technology, the medical community has benefited from a new and safe vehicle to find solutions to problems that have existed with little gain. This new technique has now provided opportunities to ignite real progress in discoveries for new clinical trials and vaccines and are progressing quickly.

According to Penn Medicine News, mRNA pioneer Dr. Drew Weissman believes, “Outside of infectious diseases, mRNA technology could be the future of protein replacement therapies, immuno-therapeutics, cancer treatments, personalized cancer vaccines, genetic diseases, and other drug development.”²

New Developments in Vaccines

In the field of vaccines, new developments are currently being made using this same COVID-19 blueprint. Since the COVID-19 outbreak, a patent has been filed for a new malaria vaccine for researchers at Yale University using RNA technology.

Guided by the model used for the COVID-19 vaccine, the malaria vaccine is being developed to achieve long-term immune protection from the Plasmodium Macrophage Migration Inhibitory Factor (PMIF) protein.³ The University of Illinois, Chicago has also been making progress in the development of an mRNA vaccine for dengue fever. And despite over three decades of research, HIV has eluded a vaccine. However, as of March 2022, a Phase 1 study began to examine mRNA technology for HIV and evaluate three experimental HIV vaccines.^4-5

Prior to Covid-19, Pfizer and BioNTech had been working on an mRNA vaccine for seasonal influenza. Previously, researchers struggled because multiple variants of the flu are factors during any given season. Before mRNA technology, the challenge was selecting the strain that was either most probable or presented the largest health risk. Using mRNA technology may now allow the ability to modify the flu vaccine quickly once the seasonal variant has been identified.⁶

Cancer Therapy

In the field of cancer, instead of using mRNA to elicit an immune response against a foreign protein, the technology is being used to make the body’s own cancer cells identifiable to the immune system. Throughout the research community, mRNA technology had been studied long before the pandemic for potential general and personal treatment plans. Dozens of clinical trials are now underway in which mRNA instructs a patient’s cells to produce protein based on a tumor’s genetic mutations which then prompts the immune system to find other mutated cancerous cells, as well as tumor cells, and attack them.⁷

Gene Therapy

In the field of gene therapy for genetic and inherited diseases, which affect small numbers, there is new hope with possible treatments and trials. Unlike vaccines which use mRNA for protection against a virus, gene therapy uses mRNA’s gene-editing ability to target abnormal areas of gene sequences that need to be deleted or corrected. One such example is amyloidosis, "a rare disease that occurs when an abnormal protein, called the amyloid, builds up in the organs and interferes with their normal function.”⁸

Previously, there was no cure and only limited treatment for this disease. Now, for familial transthyretin amyloidosis, a genetic or inherited type of amyloidosis, in conjunction with CRISPR technology, mRNA is being used to deliver gene-editing instructions to the liver, thus shutting down the production of the abnormal transthyretin (TTR) protein.⁹

The Role of Lipid Nanoparticles in mRNA Technology

With all the accomplishments that lie ahead for mRNA technology, these achievements would not be possible if not for the key component of lipid nanoparticles (LNPs). Lipid nanoparticles are recognized as a superior drug delivery platform for delivering nucleic acids, DNA and RNA.

Composed of a layer of fat, LNPs offer flexibility and protection to their payload. Since both LNPs and cell membrane structures are similar, LNPs are accepted as transport carriers into cells where they can then release their payload safely. Previously, mRNA did not have an effective vehicle to enter the body or reach its destination.

Now, mRNA has been revolutionized to deliver its payload and achieve success when used in conjunction with lipid nanoparticles. LNPs are the superior complement that allows mRNA to travel to their targeted area intact. Without LNP technology, the existence and success of mRNA vaccines would simply cease to exist.

What Role Does Microfluidics Play in this Technology?

Microfluidizer^® technology is a proven method for achieving superior, solvent-free lipid nanoparticles.

• Our processors achieve LNPs with controlled particle sizes and narrow distributions for increased product stability and improved downstream process by delivering consistent, high shear forces. Through Microfluidics’ unique Interaction Chamber™, the material is exposed to extreme shear rates thereby requiring fewer passes to achieve particle size reduction. This efficient processing provides a benefit in both time and cost.

• Our proven solvent-free method eliminates the complicated process of solvent removal which not only saves time and money, in the production process but also makes it environmentally friendly.

• Our unique top-down technology can conform to cGMP regulations which is critical for pharmaceutical and biotechnology production. Microfluidics International Corporation offers a full range of lab-scale, pilot-scale and production-scale processors which have been used by top pharmaceutical companies for decades. Our team of engineers are knowledgeable in the design, materials, and sanitary requirements needed to meet all government cGMP regulations.

• Microfluidizer^® technology is linearly scalable for consistent, repeatable results from research and development to production scale volumes. Not only can results be duplicated batch-to-batch but, through Microfluidics’ revolutionary Interaction Chamber™ system, they can also be easily replicated from benchtop results to global distribution. Thereby, as mRNA technology continues to achieve success in research and development, these successes can be easily implemented to production scale to reach their true potential.

Microfluidics International Corporation, the manufacturer of Microfluidizer^® high shear fluid processors, is a leader in the design and production of laboratory and commercial processing equipment for nano-scale material. Through superior lipid nanoparticle production, Microfluidics International can help achieve the next mRNA breakthrough.

References

• ¹ FDA approves COVID-19 mRNA vaccine that uses fundamental Penn technology
• ² COVID-19 mRNA Vaccine that Uses Fundamental Penn Technology Receives FDA Approval
• ³ Yale lab develops revolutionary RNA vaccine for malaria
• ^4-5 Beyond COVID, the Future of mRNA Is Bright | Discover Magazine
• ⁵ Clinical trials begin for three mRNA HIV vaccines
• ⁶ How mRNA Technology Could Change the World - The Atlantic
• ⁶ A universal flu vaccine may be the next big mRNA breakthrough for Moderna, Pfizer
• ⁷mRNA Is Capable of Providing Solutions Far Beyond Vaccines
• MRNA's Next Chapter Has Nothing to Do With COVID-19 Vaccines
• Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: applications, advantages and disadvantages 
• How mRNA Vaccines Could Prevent or Eliminate Infectious Diseases Beyond COVID-19
• mRNA technology promises to revolutionize future vaccines and treatments for cancer, infectious diseases | AAMC
• Drew Weissman, father of revolutionary COVID-19 mRNA vaccine, sets next target: Cancer, other viral diseases | Special-reports – Gulf News