RNA Architects
Why we invested in Sixfold Bioscience
We’ve all seen — experienced even — the power of RNA this year. It took one vaccine and a global pandemic to promote RNA from a niche area of life science to a household name. Yet, vaccines represent a mere fraction of what RNA therapeutics are capable of.
Over 4,000 diseases are caused by errors in a patient’s genetic code that lead to faulty protein production or the wrong genes getting expressed. With RNA therapeutics, genes leading to faulty protein production can be turned off through RNAi molecules while mRNA strands can be delivered to create beneficial proteins. However, in order to have a therapeutic effect, RNA must get to the relevant cells. This is where the challenges arise.
Since RNA is translated into proteins within cells, it must be delivered to the right cells to have the desired therapeutic effect. Unfortunately, RNA is extremely difficult to deliver. Current approaches only allow for delivery to a limited number of tissues, primarily hepatic (liver) tissues or local application (eg. when it is practical to use a syringe). This is because the body naturally clears molecules like the lipid nanoparticles used for RNA delivery to the liver for metabolism. For general immunity purposes, like with the COVID vaccines, this is fine. We only need to produce the spike proteins in one area before they are able to circulate. For diseases where a much finer control is needed or specific proteins in disease-cells need to be inactivated, delivery is a glaring challenge. This means RNA is only being used for diseases relevant to easy-to-target organs like the liver.
In order to unlock the full potential of RNA medicines, we must solve the delivery challenge.
Enter London-based Sixfold Bioscience, Co-Founded by Anna Perdrix-Rosell and George Foot. Sixfold is building Mergo®, a computationally-integrated platform that engineers RNA delivery vehicles to target any tissue in the body.
Given that much of what drives a delivery system to target non-liver tissues is not well documented or understood, Sixfold is taking a systematic and data-driven approach to overcoming this “black box.” Mergo® is trained on proprietary chemical libraries and outputs a customized nanoscaffold. Detailed biological readouts then immediately guide the design of the next version. It is this iterative nature that enables the system to rapidly learn the best combinations for a given tissue target and strengthens the platform with each development cycle.
Mergo’s computational integration optimizes the nanoscaffold to not only deliver RNA to the right cells, but also improve the stability of the RNA. Importantly, Mergo can drive the biodistribution of the RNA therapeutics away from liver tissue, which is a key challenge that many traditional lipid-based delivery systems run into.
A lot of what has enabled Sixfold to perform the rapid iteration cycles that are fundamental to this approach is the whole process is developed in-house, an unusual feat for a company of this size. Anna and George have built an incredibly diverse and talented team, with expertise ranging from ML/AI and small molecule synthesis through to preclinical testing.
By engineering biology in the most literal sense, Sixfold is creating customizable drug delivery systems for next-generation medicines — as an infrastructure technology and drug discovery engine.
While the team plans to partner their platforms with biopharma, they are also creating their own pipeline of RNA therapeutics in-house. Instead of enabling one-off RNA therapeutics, Sixfold’s Mergo® will enhance all RNA therapeutics, ensuring that the right medicine gets to the right cells.
We’re thrilled to partner with Anna and George in Sixfold’s seed financing, becoming one of its largest investors. This capital will help them accelerate the design and development of RNA therapeutics, allowing the power of RNA to be extended to previously inaccessible diseases. The age of RNA is just beginning.
