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Inside the Delivery Vehicles Critical
to the Success of mRNA

By Sachi Fujimori | June 2022

All precious cargo needs a reliable vehicle to get it to its final destination.

Such is the case for messenger RNA, or mRNA, an infamously fragile molecule. In fact, we would not have mRNA COVID-19 vaccines today without a lesser-known technology: lipid nanoparticles, or LNPs, the delivery vehicles that shuttle these molecules into our cells.

mRNA is a set of instructions that our cells use to make proteins. And mRNA-based therapies leverage this natural protein-making ability. When these instructions are encoding a specific protein, such as the spike on the SARS-CoV-2 virus, they can turn our cells into protein-making factories. Given the flexibility of mRNA to encode any number of proteins, this technology has the potential to uncover breakthrough treatments for rare diseases, chronic conditions, and more.

Our cells are prolific protein factories.

Protecting the instructions

But if injected alone into the body, mRNA quickly breaks down. It also can’t enter target cells in the body without a delivery vehicle. To overcome these challenges, scientists turned to LNPs, which are essentially tiny protective bubbles of fat. During the vaccine manufacturing process, the mRNA instructions are encapsulated in these lipid nanoparticles.

It’s like a delivery truck protecting cargo as it drives down the highway. The lipid nanoparticle shields the mRNA from everything that may destroy it.

When the mRNA COVID-19 vaccine is injected into the arm, these LNP delivery vehicles shuttle the mRNA instructions into cells. The instructions are then unloaded, and the cell can make the spike protein, which induces immunity against the spike protein encoded by the mRNA.

“All under one roof”

As Pfizer expands its mRNA programs into new potential vaccines and therapies, LNPs will continue to be critical to the success of these potential medical advances. In addition, the development of mRNA and LNP technology for new therapeutic areas will benefit from other innovations, including in how LNPs are formulated and manufactured.

Much of this early work is done by scientists like Warne who specialize in biological formulation in Pfizer’s Pharmaceutical Sciences Group. Like a recipe developer who perfects a dish before it can be prepared by many, Warne and his colleagues work to refine the process of creating a new vaccine or therapy while maintaining rigorous quality control and safety standards. “We’re protein chemists, pharmaceutical scientists, and chemical engineers. We figure out exactly how to make the therapies and vaccines that we are developing,” says Warne.

Once they’ve developed the final recipe, a drug or vaccine formula, they hand this knowledge over to the manufacturing group, where experts determine how it will be made at mass scale. “We don’t just throw it over the wall. It’s in our best interest to ensure they fully grasp the recipe and that we’re all in this together. That’s the advantage of having us all under one roof,” says Warne.

Custom delivery trucks

In just two years, Pfizer has gained critical expertise in manufacturing messenger RNA and its delivery trucks, LNPs.

The challenge now is designing the delivery trucks to reach new cell types and carry different types of cargo. To treat rare genetic diseases, for example, the LNPs will need to reach a particular tissue or organ in the body, such as the liver, kidneys, or heart. “Depending on what you’re trying to deliver and where you wish to deliver it to, you may need a different approach or different car,” says Warne.

As Pfizer expands its mRNA capabilities, its decades of experience in vaccine and drug manufacturing will continue to prove critical in advancing innovative technologies.

The success story of the mRNA COVID-19 vaccine is only the beginning. As we enter this new era of mRNA medicine, Pfizer scientists, engineers, and talent around the globe will continue to apply their experience, agility, and focus to delivering breakthrough treatments to improve patients’ lives.