However, it is probably in vivo mRNA vaccination that has most recently and noticeably underscored the safety advantages of mRNA-based interventions 10. In vivo mRNA delivery has been employed for interventions such as protein replacement therapies, cell reprogramming and gene editing, amongst others 10. Clinical applications of mRNA span across multiple indications, encompassing both in vivo and ex vivo approaches. Pharmaceutical companies such as Sanofi, Sangamo, Pfizer, Myeloid TX, Carisma Therapeutics, Moderna, and AstraZeneca have invested money to advance their presence in the mRNA therapeutics space 6, 7, 8, 9. Moreover, transient expression is a feature that can be exploited when addressing safety concerns associated with long-term expression of an experimental transgene 4. In this way, mRNA carries a reduced risk of genotoxicity because it is unable to integrate into the host genome 4, 5. Unlike DNA-based therapies, mRNA becomes functional once it reaches the cytoplasm, resulting in transient expression of a therapeutic protein. Amongst other advantages, mRNA offers drug developers an efficient, easy-to-design, and safer platform for gene transfer compared to DNA transfection or viral vector transduction 3. The use of mRNA as a vehicle for therapeutic application has become more practical with the advancement of novel nonviral delivery methods 1, 2. Results demonstrate that the device can operate at a wide range of cell and payload concentrations and that ultra-fast compressions do not have a negative impact on T cell function, making this a novel and competitive platform for the development of ex vivo mRNA-based gene therapies and other cell products engineered with mRNA. Here, we describe efficient delivery of mRNA into T cells, natural killer (NK) cells and hematopoietic stem and progenitor cells (HSPCs), three human primary cell types widely used for ex vivo gene therapy applications. ![]() In the device, cells flow through a ridged channel that enforces a series of ultra-fast and large intensity deformations able to transiently open pores and induce convective transport of mRNA into the cell. We designed a novel microfluidic device that allows for efficient mRNA delivery via volume exchange for convective transfection (VECT). Amongst other applications, mRNA can be employed as a platform to deliver gene editing molecules, to achieve protein expression as an alternative to enzyme replacement therapies, and to express chimeric antigen receptors (CARs) on immune cells for the treatment of cancer. ![]() ![]() Messenger RNA (mRNA) delivery provides gene therapy with the potential to achieve transient therapeutic efficacy without risk of insertional mutagenesis.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |