FlashRNA®, a cutting-edge RNA delivery system for Cell & Gene Therapy
FlashRNA® is a game-changing tool for gene and cell therapies due to its ability to engineer multiple cell types, including difficult-to-transduce cells. This tool demonstrates high transduction rate without compromising viability and the original cell phenotype, making it a safe and reliable tool for gene and cell therapies.
LymphARN, First-in-Human trial in 2025: mRNA therapy as a curative treatment for secondary lymphedema
LymphARN clinical trial: in vivo delivery of both Apelin and VEGF-C mRNAs, thanks to FlashRNA® used as a curative treatment
Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return and swelling of the extremities. The accumulation of undrained lymphatic fluid leads to fibrosis and fat tissues deposition in the affected arm or leg.
The condition can be hereditary or occur after cancer surgery and lymph nodes removal. 10% to 15% of women develop lymphedema after surviving breast cancer. It is a common condition that affects more than 120 million people worldwide and cause significant morbidity.
FlashRNA® (APLN and VEGF-C) reduces lymphedema by restoring lymphatic vessels and suppressing dermal backflow
Secondary lymphedema is induced in mice by mastectomy of the 2nd mammary gland, associated with brachial and axial lymphadenectomy. FlashRNA® is intrea-dermally injected in the limb at day 10.
Mice were injected 10 days post-surgery. Lymphedema swelling reversion was observed from 1 day after FlashRNA® treatment.
The complete regression was obtained 11 days post-injection despite the transient expression of the 2 transgenes. Natural regression of the pathology occurs after 21/28 days in mice.
After lymph node resection, mice exhibit a reduction of lymphatic drainage associated with visible dermal backflow (arrows).
4 days post FlashRNA® treatment, lymphatic vessels are restored, and dermal backflow is suppressed (well defined vessels).
Source : Creff J, et al. EMBO Mol Med. 2024
This project was funded by the European Union’s Horizon 2020 research and innovation program under grant agreement no. 874708.
FlashRNA® : a versatile tool for safe and efficient transduction of various cell types
FlashRNA® enables to transduce more than 90% of activated T-cells
T cells isolated from human PBMCs modified with increasing doses of FlashRNA® show a very high level of expression at low dose. A progressive increase in protein expression is also noted with escalating doses of FlashRNA®.
FlashRNA® is titrated with a p24 ELISA assay and dose unit is expressed in pg of p24/cell.
More than 90% of activated T cells express ZsGreen 48h after transduction.
In addition, engineered T cells maintain expression of the CD3 and CD25 markers showing that cell phenotype and cell viability are preserved.
FlashRNA® technology achieves high transduction efficiency in hard-to-transduce cells, such as human CB-HSPCs
Hematopoietic Stem and Progenitor Cells (HSPCs) isolated from Cord Blood (CB) and engineered with a dose range of FlashRNA® solution demonstrate a high level of expression at low doses and a dose-response increasing level of expression. About 99% of HSPC express ZsGreen protein 48h after transduction, starting at a dose as low as 0.1 pg of p24/cell*.
*FlashRNA® is titrated with a p24 ELISA assay and dose unit is expressed in pg of p24/cell.
Engineered HSPCs maintain expression of the CD34 marker compared to untransducted cells, showing that cell phenotype is preserved, as well as cell viability.
FlashRNA® as a Highly Efficient RNA delivery tool to express gene in human induced-Pluripotent Stem Cells (hiPSC)
Human induced-pluripotent stem cells (hiPSC) engireered with increasing doses of FlashRNA® show a very high level of expression even at a low dose contrary to lipofection. Transduction efficiency with FlashRNA® technology is close to 100% in iPSC, allowing cell reprogramming and gene editing.
FlashRNA® efficiently modifies all hiPSCs while preserving their phenotype and viability. Cell proliferation rate is maintained compared to non-transferred cells.
Mianné J, et al. BMC Biol. 2022
FAQ
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.
Is it possible to target a specific cell type?
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® suitable for clinical use?
Yes, FlashRNA® is produced using scalable, GMP-compliant manufacturing processes, making it ready for therapeutic applications. FlashRNA® has already been produced as a Drug Product, to be used for a First-in-Human phase 1/2 clinical trial in 2025 (LymphARN trial, to treat secondary lymphedema).
Can FlashRNA® be used to deliver gene editing systems?
Yes, nuclease mRNA and single guide RNAs can be packaged within the same particle. FlashRNA® has already been used in many types of primary cells, from stem cells to immune cells, as well as human induced pluripotent stem cells (iPSCs), showing an efficient gene editing without compromising cell viability or the differentiation capacity of stem cells.
Which dose of FlashRNA® do I need to use on my cells?
The optimal dose of FlashRNA® for your cells depends on several factors, including the specific application, cell type, and experimental context. Doses are expressed in pg of p24 protein per cell. Typically for ex-vivo transductions, doses between 0,1 pg and 5 pg p24 / cell are sufficient to obtain a very efficient expression.
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