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Jake Lesnik, VP of Business Development at Mekonos, discusses the current challenges faced by therapeutic developers in delivering molecular cargo into cells, highlighting the drawbacks of conventional methods, such as viral vectors and electroporation, citing safety concerns, manufacturing complexity, and viability issues as significant obstacles.
To start with, please could you introduce yourself ?
My name is Jake Lesnik. I’m the Head of Business Development at Mekonos. At Mekonos, I’m responsible for our commercial strategy and external partnering.
What challenges associated with delivery of molecular cargo into cells are currently facing therapeutic developers right now?
So right now, there are really two conventional delivery methods. The first is viral vectors, and there’s quite a number of challenges with these. Most notably, in December of 2023, the FDA launched an investigation of commercial CAR -T therapies because of safety concerns caused by the random integration of using viral vectors. So that’s a big safety consideration there. Viral vectors also bring a lot of complexity into manufacturing as well.
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The other most popular non-viral vectors method is electroporation, which is essentially electrocuting cells until they have holes in them, and that is not very good for cell viability. So, the viability is a big challenge there among other concerns.
How are these challenges significant? What bottlenecks, obstacles or issues do developers encounter because of these challenges?
I think, for sure, the safety concerns are paramount. We’re dealing with these advanced therapies, and we want them to be as safe as possible. They have huge curative potential, but these powerful cell therapies can cause powerful effects in the body, so the safety concerns for when things go wrong is definitely one of the biggest factors.
Then when you look at manufacturing, these are very complex cell therapies. Autologous cell therapies require taking a patient’s cells from the body, processing them, typically at a third-party location, bringing them back to the patient, within a reasonable period of time, also where time is of the essence.
When you have to add in additional steps like GMP manufacturing of viral vectors, that’s a big concern, and then of course we want to have the cells be as effective as possible.
When it comes to efficacy, a lot of the time when you’re dealing with viability issues in these cells, the cells that have the strongest potential to cure the patient are the most fragile. When you have a harsh delivery technique like electroporation, the very cells that you want may be the ones that don’t survive.
These are significant challenges for the field, and collectively are why we see tremendous interest in looking for next-generation technologies with better new delivery solutions.
Could you tell us a bit about how Mekonos addresses these challenges? What is it about your proprietary platform that supports therapeutic developers in the CGT space?
At Mekonos, we’re developing a completely novel method for ex vivo delivery of payload into cells, and this is a non-viral system that avoids the difficulties of using viral vectors.
With a completely novel approach, we use silicon nanoneedles on a chip to directly deliver payloads into cells, which has a number of unique advantages associated with it.
The Mekonos platform addresses these challenges because it offers an unprecedented amount of control and precision in the delivery of payloads into cells. We’re actually able to target the payloads to the nucleus, so we have this targeted intracellular delivery with very high efficiency.
This gets around some of the safety concerns that come with random integration – we’re actually able to enable advanced gene editing where you can target the delivery of a payload into a safe harbor locus and avoid some of these safety concerns.
We also have the ability to address the viability concerns because our nanoneedles are delivering payloads through a single pore in the cell. This is extremely well tolerated and this gentle method actually means that more of the cells that you want will survive the process.
Our approach also enables dose control in a way that is not possible with conventional delivery methods. We load the payloads onto the needle, we can actually control the concentration and the release of the payloads into the cell, and so this also enables the potential for safer therapies.
Overall, the Mekonos platform enables single cell delivery at scale, and this has huge benefits in the precision of the delivery for both cell therapy development and manufacturing.
Where do you see the field in 5–10 years’ time, and how might technology like the platform you have at Mekonos fit into the technology landscape of tomorrow?
I think again, the challenges with today’s conventional delivery methods are well known, so in the next 5–10 years, we really see an opportunity for new delivery technologies to displace the existing ones and offer a number of superior benefits, including the ability to streamline manufacturing.
You can now have these high efficiency approaches that can be automated, be much more scalable, and we can also unlock new cell therapy types today, with new cells and new types of cargos that are more complex and larger, to really unlock new types of cell therapies for the field.
Ultimately, these new technologies like Mekonos, may even be able to enable point of care manufacturing, where cell therapies can be manufactured the same place where the patients are being treated.
Do you have any final comments or thoughts you would like to share about the technology, the industry or where the conversation may be headed as we enter 2024?
At Mekonos, we’re super excited about 2024. We’ve recently completed the construction of the MVP unit of our platform, so we’re really excited to start putting that into use with a number of our active partnerships at the proof-of-concept stage with biopharma partners.
We’re really excited about the ability of our technology to revolutionize how cell therapies are developed and manufactured, and we’d love to hear from cell therapy developers about any delivery challenges that they may have, whether that be fragile cell types, or complex payloads, to see how we can help drive forward their cell therapy programs.
This interview has been produced in partnership with Mekonos.
