A commitment to research of new delivery tools for a decade
- Current lentiviral vectors, which deliver DNA integrated into the genome and result in stable expression, are a leading delivery method for treatment of certain genetic diseases and CAR-T cancer immunotherapy, which require long-term gene expression.
- However some applications are not well suited to genome-integrating approaches—e.g., gene editing, next generation immunotherapy, due to potential toxicity. The delivery of nuclease[s] or antigens using DNA tools leads to cell toxicity due to high and persistent expression of nucleases/proteins.
- Moreover, the permanent genetic modification remains a focus of significant regulatory oversight since it can induce insertional mutagenes is resulting from random integration of vector DNA into the host DNA when using DNA delivery.
To date the development of safe approaches that transiently express an RNA of interest in primary cells have been a challenge.
“Our new company is committed to developing non integrative delivery technologies in order to overcome DNA-mediated limitations. Such tools are required for gene-editing approaches that need only a transient delivery of the editing machinery”
Pascale Bouillé, PhD, CEO of Flash Therapeutics.
RNA delivery capabilities mediated by new chimeric lentiviral particles called LentiFlash®
LentiFlash® technology is a new chimeric system combining the respective properties of a bacteriophage and a lentiviral particle. The resulting particle combines the best entry efficiency into cells both in vitro and in vivo and the safest genetic material delivery, namely RNA.
RNA delivery mediated by a lentiviral particle is an attractive approach that leverage positive clinical proof of concepts provided by the parental lentiviral vector in the past and provide a disruptive transient and safe cell engineering. The following table compares lentiviral vectors, LentiFlash RNA delivery system and RNA transfection:
Cell transduction mechanisms with lentiviral vectors and LentiFlash technology
The engineered chimeric LentiFlash® particle
Flash Therapeutics has developed a new non-viral RNA-delivery packaging system based on a chimeric lentiviral platform. This new product marketed under the brand name LentiFlash® has been patented by Flash Therapeutics and its properties and derived applications have been published by the Nature Publishing Group in Molecular Therapy — Methods & Clinical Development (2015) 2, 15039
To construct this new lentiviral platform, Flash Therapeutics has combined the respective properties of a bacteriophage coat protein and the lentiviral particle:
- The wild type HIV packaging sequence was deleted and replaced by a bacteriophage stem-loop repeats
- The sequence of the bacteriophage Coat gene was inserted into the NucleoCapsid sequence in the helper packaging system
The resulting particles exhibit the same structure but contain more than 6 RNA copies versus 2 for classical lentiviral vectors. Furthermore, these new particles do not contain the required elements to perform reverse transcriptase or integration. The RNA will be directly translated into proteins once delivered into the cell cytoplasm.
Properties of chimeric RNA delivery LentiFlash® particle
The delivery properties of this new RNA delivery system are the following:
- RNAs are rapidly bioavailable, leading to high and short-term expression of the transferred messenger.
- LentiFlash® is a versatile and efficient cell transfer system for mRNA or other types of RNAs delivery (in vitro in immortalized, primary & stem cells and in vivo in mice)
- The high efficiency of RNA transfer by LentiFlash® is most likely related to an increased ratio of RNA to particle content, resulting in directly detectable and significant biological activity
Our intellectual property
Integrative lentiviral vectors
Flash Therapeutics is a biotech company set up in 2005 which has first developed a state-of-the-art technology for lentiviral vectors production. Vectalys has initially built its portfolio of patents on the production process and the resulting vector quality. The first two patents families are then respectively focused on the composition of the lentiviral batch and the resulting consequences on the target cells.
Flash Therapeutics has then focused on the development of non-integrative delivery methods based on its lentiviral platform. A third patent family was filed in 2015 to protect this new generation of bacteriophage-driven RNA packaging system using Coat-retrovirus chimeras.
Sub-licence of our technology
Flash Therapeutics has sub-licensed in 2016 its new LentiFlash® technology and rights to a clinical-stage biotechnology company, FlashCell, for a wide range of therapeutic applications including immunotherapy and gene editing approaches. In 2017, FlashCell carried out research programs to complete the intellectual portfolio and identify its own clinical programs. Two additional patents families have been filed in gene-editing and immunotherapy fields in 2016.
If you are interested in our LentiFlash® technology and would like to obtain a sub-license, please contact us. We are constantly looking for new partners for the development of our innovative technology in the gene transfer market.