The rapid evolution of cell and gene therapy calls for innovative gene delivery systems, able to respond effectively to the various strategies that can be envisaged, from gene expression to gene correction/replacement. Although DNA-based therapies using integrative lentiviral vectors and AAV have become widely available on the market, RNA-based therapies offer greater versatility and cover a wide range of applications with minimal risks. These therapies are particularly well suited to treat or prevent a wide variety of diseases. They are designed for applications where transient expression is safer, such as stimulating a cellular process, modifying a genetic sequence or directing cells towards a specific pathway. Depending on the disease, the delivered RNAs are designed to align with the selected therapeutic strategy, whether gene editing, regenerative medicine or immuno-oncology. RNA optimization varies according to the target cells, the ex vivo or in vivo approach required, the genes of interest, and the intended level and duration of expression.

Organoids are three-dimensional stem cell-derived cell culture systems capable of mimicking the architecture and function of real organs. These miniature organ-like structures are invaluable tools for biomedical research thanks to their ability to closely mimic the in vivo environment. Despite persistent difficulties and the unmet need for new therapeutic strategies, organoids have emerged as a promising animal-free tool, revealing patient heterogeneity and enabling in-depth preclinical therapeutic screening. These tools are revolutionizing drug discovery, personalised medicine, regenerative medicine, and offering new strategies for genetic modification. See the datas.

Flash BioSolutions has developed a revolutionary RNA technology, called FlashRNA®, to transfer RNAs safely and efficiently thanks to its unique features. It can deliver multiple types of RNAs in a highly specific way via a patented encapsulation method. Thanks to a robust multilayer particle, the RNAs are protected from degradation, delivered very efficiently into the cytoplasm of any cell types and immediately available for a rapid translation into proteins, without any risk of cell damage or phenotype alteration. FlashRNA®, which enables precise and efficient control of gene expression and modulation, has demonstrated its ability to transfer RNA and lead to efficient protein expression in organoids to be further used for various studies.

FlashRNA® is thus proving useful for improving the accuracy of disease modelling, drug development studies and screening, and even the development of personalised medicine. FlashRNA® has also demonstrated the ability to edit the genome of iPSCs, without inducing toxicity or adverse effects on their differentiation capacity. This efficient and safe delivery paves the way for its further use for specific applications such as genome editing on pluripotent stem cells and therapy.

In summary, FlashRNA® represents a breakthrough for cell and gene therapy, offering a powerful, safe and flexible delivery system for organoids, iPSCs and in vivo approaches. Its ability to induce efficient and precise genetic modifications positions it as a leading technology for advancing therapeutic strategies, with promising implications for all therapeutic areas. Furthermore, FlashRNA®’s existing cGMP-compliant production capabilities and rapid customization allow to be promptly adapted to a variety of therapeutic needs.

For more data download the poster here.

Recent advances in gene and cell therapy highlight the complex challenge of delivering therapeutic agents tailored to specific diseases. While DNA-based therapies have gained notoriety (ILV & AAV administration), the focus is now shifting to RNA-based therapies as a versatile alternative, that can target undruggable pathways⁽¹⁾. RNA therapeutics are a rapidly expanding class of medicines that will change the standard of care for many diseases and bring personalized medicine up to date. It is a disruptive therapeutic technology. This shift is driven by the need for a universal delivery tool that can be used for a wide range of applications while minimising risks, particularly genotoxicity. RNA-based therapies thus offer the flexibility required to target specific therapeutic applications requiring transient expression, whether for gene modification, regenerative medicine or immuno-oncology. This field of application encompasses triggering cellular processes, modifying genetic sequences or directing cells along specific differentiation pathways. Once optimised, these genetically modified cells become effective medicines, illustrating an innovative approach in the landscape of next-generation 2.0 therapies⁽²⁾.

To overcome the safety limitations of AAV and lentiviral vectors, a revolutionary RNA delivery tool called FlashRNA® (formerly LentiFlash®) has been developed, providing safe and effective solution. This innovative bacteriophage-lentivirus chimera combines the RNA packaging system of bacteriophages with the structure of lentiviral particles, delivering several species of RNA in a single FlashRNA® particle⁽³⁾. This not only protects the RNAs from degradation but also enables them to be delivered efficiently into the cell cytoplasm, thanks to VSV-G pseudotyping that ensures broad tropism or alternatively use of particular pseudotyping to target specific cell types. RNA bioavailability and protein translation is fast, without any risk of integration into the host genome. As a result, transduction by FlashRNA® does not result in GMO generation. Furthermore, the packaged RNAs are devoid of any lentiviral sequence and are from biological origin: indeed, as they are synthesized in human producer cells, they undergo all cellular post-transcriptional modifications, thus preventing adverse immune responses upon delivery into target cells.

To highlight the three innovative therapeutic strategies – gene editing, regenerative medicine and immuno-oncology – we invite you to discover concrete examples that illustrate each of these approaches.