mRNA therapeutics are now expected to become the third major class of drugs. But converting their promise into reality, just like what happened with electric vehicles, is not without technical challenges.
In the case of electric vehicles, their sales only really took off once the complex new battery technologies which enabled high-performance together with extended travel range was delivered.
A similar process is now unfolding in the world of mRNA therapeutics, which promise new ways to treat many medical problems at their root and opening the door to personalized medicine.
mRNA-based medicines have the potential to be quick to design and develop, cost effective, relatively simple and quick to manufacture, and able to target previously undruggable pathways. Witness the extraordinary success of mRNA vaccines against COVID-19.
But these revolutionary mRNA therapies have one key technical challenge to be overcome before they are practical – how to package up and deliver the susceptible mRNA through the body and into cells and ensure the RNA is converted into the desired end-product efficiently and without unwanted side effects from the carrier.
Importantly taking the car analogy a step further, such an ideal drug-delivery ‘chassis’ now exists. This thanks to recent advances made in exosome technologies.
How so?
In the initial stages of this emerging mRNA age with mRNA vaccines from Moderna and BioNTech, synthetic lipid nanoparticles (LNPs) were used to package up and deliver mRNA. Recent studies undertaken by the medical researchers have found that synthetic LNPs are immunogenic, highly inflammatory and came with the risk of tissue damage.
For a vaccine product that is administered only a small number of times – the LNP immunogenicity acted as an adjuvant and was an advantage, whilst the inflammation and tissue damage associated with the LNPs was outweighed by the potential severity of serious COVID-19 infection.
Exosomes are nature’s RNA delivery vehicles: nano-scale particles released and received by cells around the body, acting as a biomolecule parcel delivery service with cargo RNA in tow.
Evidence is building that exosomes do not have the shortcomings of synthetic LNPs and would be a preferred drug-delivery option for many mRNA therapeutics over LNPs.
To understand this, it is important to understand that the drug-delivery requirements for mRNA vaccines (such as Moderna Spikevax and Pfizer Comirnaty COVID-19 vaccines) and mRNA therapeutics differ in several critical and challenging ways. Here goes …
In mRNA vaccines, mRNA for the viral protein is loaded inside LNPs. When injected into the patient’s muscle, some of the LNP-mRNA substance enters nearby cells and causes some cells to produce the viral protein ‘in situ’ (that is, inside the patient’s body). This ‘foreign’ viral protein is then exposed to the outside of the cell and then triggers the patient’s immune system, stimulating immune-signal amplification pathways that convert a small amount of exposed viral protein (antigen) into a potent immune memory against future infection.
A therapeutic mRNA product, on the other hand, achieves additive gene therapy by delivering the required RNA sequence for the gene-product into target cells, so that the cell’s own protein-producing ribosomes transcribe the RNA in situ and produce the desired gene-product. The RNA therapeutic must produce as much as a 1,000-fold higher level of gene-product as compared to mRNA vaccines.
Whilst immunogenicity is a benefit with a vaccine product, a therapeutic mRNA product needs to avoid immunogenicity and producing inflammation.
We have now seen that LNPs are fine as the nano-carrier for RNA vaccines but poorly suited to RNA therapeutics.
Given that there are only really two nano-sized particles currently available that can have mRNA loaded into them – LNPs and exosomes – this brings us to exosomes as the potential game-changer nano-carrier for mRNA therapeutics.
Until very recently, the manufacturing technologies required to harness exosomes as a more natural drug-delivery chassis had not been invented.
This growing validation of, and excitement about, exosomes combined with the bright future for mRNA therapeutics is a positive development for ASX-listed healthcare technology company Exopharm Limited (ASX: EX1).
Exopharm has, over time, developed a tool chest of seven exosome-related manufacturing technologies – each solving an essential challenge in exosome manufacture. This intellectual property and knowhow is now validated by an extensive library of data and test results.
Exopharm’s technologies and validation data now support exosomes as a potential drug-delivery chassis for important mRNA therapeutic products.
Exosomes, which can be designed and manufactured to target selected cells/tissues/organs, offer multiple advantages over LNPs for RNA therapeutic products.
Exopharm’s technologies solve multiple critical drug-delivery challenges, specifically:
- Solving the isolation and purification problem in a high-scale and reproduceable process using Exopharm’s patented LEAP technology
- Exopharm’s exosomes or extracellular vesicles (EVs) are homogeneous from batch to batch
- An ability to efficiently load mRNA and other types of RNA into EVs and biological activity at useful levels
- Exopharm’s EV are highly characterised
- Exopharm can add tissue targeting technology (EVPS) to the exosomes
- Testing shows that Exopharm’s exosomes are ‘immune silent’ in animal studies
- Testing shows that Exopharm’s exosomes are non-toxic in animal studies.
Exopharm is today well-placed to leverage its technology and knowhow in the exciting field of mRNA therapeutics.
The company continues to prove up its exosome-related manufacturing technologies and build a leadership-position in the biopharmaceutical industry.
The combination of mRNA together with exosomes opens up the promise of new ways to treat many medical problems at their root with a new class of drugs able to target previously undruggable pathways.
Tony Farnham is a financial markets veteran and Analyst/Financial Writer at The Capital Network.
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