Immunotherapy and FlashRNA®: a perfect fit
FlashRNA® is ideally suited for a wide range of immunotherapy approaches, including therapeutic cancer vaccination and prophylactic vaccination against infectious diseases. With its low intrinsic immunogenicity combined with an efficient RNA transfer and a high payload capacity, it allows both the expression of multiple immunomodulation factors (like tumor-associated antigens, cytokines, check point inhibitors …) and the gene editing of immune cells to enhance their immunotherapeutic potential.
FlashRNA®-mediated antigen delivery induces rejection of progressive tumors
FlashRNA®-MAGEA3 is injected intradermally into mice 16 days after the implantation of a tumoral mouse cell line expressing MAGEA3 (Renca). Rejection of progressive tumors is observed directly after injection of FlashRNA®, showing the potential of FlashRNA® in oncology, as a cancer vaccine.
FlashRNA® is a tool of choice to engineer T cells by gene editing
FlashRNA® can mediate very efficient gene editing using the CRISPR/Cas9 system (lien vers page gene editing) as it can package and deliver both guide RNA(s) and Cas9, with a high safety profile thanks to its transient nature. Gene editing of human primary T cells is used in many immunotherapy approaches: for example, allogeneic Chimeric Antigen Receptor (CAR) T cells strategies require to knock-out the endogenous T cell receptor (TRAC), and blocking of PD-1/PD-L1 interaction has shown promising results in cancer immunotherapy, overcoming tumor cell evasion of the T cell immune response.
High gene disruption rates could be achieved for TRAC and PD-1 genes in human primary T cells using FlashRNA® to deliver a guide RNA targeting TRAC or PD-1 gene respectively and the Cas9-coding mRNA in a single step.
In vivo FlashRNA® injection does not trigger an inflammatory response
FlashRNA® does not lead to significant inflammation factor secretion after intravenous or intra-articular injection in mice, as all secreted inflammatory cytokines (IL-6, TNFa, IL-1b) are quantified below the detection threshold. As a result, immune response obtained from FlashRNA®-mediated expression is solely attributable to the expressed antigens.
FAQ
Is it possible to target a specific cell type with FlashRNA®?
Engineering the FlashRNA® particles to modify their tropism is definitely possible, as has already been demonstrated with similar particles. It is one of our main R&D projects, and we are working on it with the goal of using FlashRNA® to target any given cell type after direct in vivo administration.
Is FlashRNA® capable of engineering difficult-to-transduce cells?
We achieve excellent transduction rates for all cell types, including those difficult to transduce, such as primary cells and stem cells. For difficult-to-transduce cells or sensitive cells, we recommend using the Premium production grade to achieve the highest transduction efficiency.
What is the maximum RNA payload capacity of FlashRNA®?
FlashRNA® technology supports a high payload capacity, enabling the delivery of both small and large RNAs. Specifically, it can deliver multiple RNA molecules, including large RNAs up to 10 kilobases (kb) in length. This makes FlashRNA® suitable for complex applications such as cell reprogramming, gene editing, and immunotherapy, where the simultaneous delivery of several and/or large RNA molecules is required.
How many RNA can be delivered with FlashRNA®?
We have been able to transfer 4 different genes so far, but this is not the limit.
Is FlashRNA® redosable?
Yes, FlashRNA® has been tested in vivo, with up to three successive injections, without generating toxicity or a non-specific immune response.
Contact us
Do you have a project in mind? We’d love to hear from you!
