Comparison of different gene addition strategies to modify placental derived-mesenchymal stromal cells to produce FVIII.

ABSTRACT:

Introduction

Placenta-derived mesenchymal cells (PLCs) endogenously produce FVIII, which makes them ideally suited for cell-based fVIII gene delivery. We have previously reported that human PLCs can be efficiently modified with a lentiviral vector encoding a bioengineered, expression/secretion-optimized fVIII transgene (ET3) and durably produce clinically relevant levels of functionally active FVIII. The objective of the present study was to investigate whether CRISPR/Cas9 can be used to achieve location-specific insertion of a fVIII transgene into a genomic safe harbor, thereby eliminating the potential risks arising from the semi-random genomic integration inherent to lentiviral vectors. We hypothesized this approach would improve the safety of the PLC-based gene delivery platfor

SUBMITTER: Ramamurthy RM 

PROVIDER: S-EPMC9800010 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature