Gene-modified cell therapy (GMCT) represents the most effective platform for many patients with advanced disease. These therapies, however, are held back by inefficient development processes and manufacturing scales that are limited to a minute fraction of the relevant patient populations due to current gene delivery methods such as viral vectors. Simulation is helping to accelerate this development process and advance cell therapy.
Indee Labs is a Y Combinator company spun out of the Australian National Fabrication Facility. The team is developing novel gene delivery technology that uses ANSYS computational fluid dynamics solutions to gently and efficiently deliver genetic materials such as CRISPR to your immune cells. Indee Labs views gene delivery as the most problematic step in developing and manufacturing GMCTs since a global shortage in viral vectors has led Big Pharma to invest hundreds of millions of dollars into their own manufacturing facilities.
Microscopic Vortices Enable Cancer Cures
The core invention happened by accident. We were looking at using microfluidic devices for separating red and white blood cells from blood using post arrays, sort of like a microscopic Plinko Board. In order to raise throughput up to clinical scales, we needed to increase flow rates, which led to the question, “What is the highest flow rate a cell will tolerate?” This led to the discovery that microfluidic vortex shedding or specialized fluid dynamics could be used to gently and temporarily open holes in a cell membrane without affecting cell viability.
Discovering a method for poking temporary holes in the cell membrane in an academic environment is very different from engineering cancer killing immune cells on a large scale. Plus, there is an entire range of genetic material you can delivery to cells to modify them, such as RNA, DNA, proteins and/or various complexes.
We initially focused on mRNA since it only requires cytosolic delivery, but can be used to engineer cells in a temporary, long-lived and/or permanent manner. Put simply, mRNA was the lowest hanging fruit with the most utility. Now that our mRNA protocols for T cells and peripheral blood mononuclear cells are largely developed, we are looking at different use cases such as CRISPR complexes and large DNA plasmids.
Simulating Vortices for Efficient Immune Cell Engineering
Generating the fluid dynamics required to engineer immune cells requires semiconductor prototyping techniques, since the devices are operated at pressures around 8 to 10 atmospheres, or roughly 120 to 150 psig. Semiconductor processes are great for prototyping robust microfluidic devices; however, they require 6 to 8 weeks of iteration time. Thus, we needed a faster way to examine different device designs that was more scientific than our current ‘hypothesis followed by experiment’ or ‘guess and check’ methodology.
That is where ANSYS Fluent and ANSYS HPC packs saved us. We were able to use the ANSYS Startup Program along with Rescale’s HPC platform powered by the AWS credits we got from Y Combinator to simulate our existing designs. This allowed us to understand how to optimize the designs for efficient immune cell engineering roughly 6 to 8 times faster than the experimental process, with roughly a 10-fold reduction in direct costs per design.
We are just getting started with simulation and high-performance computing, so we look forward to utilizing all our ANSYS HPC packs to run a full parameter sweep in the near future and continue our work with gene-modified cell therapy.