Delivery, delivery, delivery!

Dr Jennifer Doudna opened the last American Society of Gene and Cell Therapy Annual Meeting in Washington by highlighting the current challenges of gene editing :
• Delivery
• Controlling repair pathways
• Ethics

Currently, to deliver and express nuclease tools into target cells, most studies used either electroporation or viral vectors. In both cases, efficient resulting gene editing was reported in many applications such as HIV, lysosomal storage disorder, beta thalassemia…

 

Safety is a major concern for defining a delivery tool :

Because safety is a major concern for defining a delivery tool such as a drug transporter, as long as the chosen vectors are able to integrate throughout the genome, the risk of gene activation and inactivation at insertion sites can be mitigated but not eliminated. This point encourages scientists and clinicians to switch towards non-integrating delivery tools such as electroporation and to use genetic material unfit for integration such as RNA.

Consideration of modified cells phenotype :

The other main consideration to take into account when making this choice is the resulting modified cells phenotype (Hmitou et al., ASGCT 2016), including biomarkers characterization and engraftment capabilities. Several presentations at the ASGCT meeting have highlighted the relationship between low clinical benefits on animals and engraftment efficiency following RNA electroporation of T cells (Schiroli et al., ASGCT 2016). Determining assays that can be used to predict whether the engraftment will occur or not depending on the cell’s phenotype following gene delivery remains a real challenge.

A new tool for efficient RNA delivery :

To combine delivery efficiency and cell preservation, Vectalys has developed a new game-changing class of RNA carriers called LentiFlash. This innovative particle is a non-viral RNA-delivery packaging system based on a chimeric lentiviral platform which combines the respective properties of the lentiviral particle and the bacteriophage MS2. The resulting RNA-delivery particle is a versatile and efficient cell transfer system for mRNA or other types of RNAs delivery both in vitro and in vivo. Considering therapeutic applications, the RNA Lentiviral Particles (RLP) have shown efficiency for the delivery of genetic information in genome editing and immunotherapy. Furthermore, its short-term and efficient RNA expression could also be useful in several other applications, such as vaccination and immunotherapy.

We hope you found this article interesting, please feel free to provide us with your comments below. To find out more about LentiFlash, click here.

References:

Preserving CD4+ T-Cells Phenotype and Function Upon Ex Vivo Lentiviral Transduction. Isabelle Hmitou, Amani Ouedrani, Lounes Djerroudi, CécileRoudaut, Laure Caccavelli, Tayebeh S. Soheili, Isabelle André-Schmutz, Marina Cavazzana, Fabien Touzot (ASGCT 2016).

Correction of SCID-X1 by Targeted Genome Editing of Hematopoietic Stem/Progenitor Cells (HSPC) in the Mouse Model. Giulia Schiroli, Pietro Genovese, Valentina Capo, Maria C. Castiello, Luisa Albano, Michael C. Holmes, Anna Villa, Giovanni Sitia, Angelo Lombardo, Luigi Naldini (ASGCT 2016).

 

 

Pascale Bouillé CEO of Flash Therapeutics

 

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