A fusion of minicircle DNA and nanoparticle delivery technologies facilitates therapeutic genetic engineering of autologous canine olfactory mucosal cells.

Alexander M Delaney,Nicolas Granger,Darren R Carwardine,Divya M Chari,Arwa F Al-Shakli,Christopher F Adams,Jon Sen,Alinda R Fernandes

doi:10.1039/c7nr00811b

Abstract

Olfactory ensheathing cells (OECs) promote axonal regeneration and improve locomotor function when transplanted into the injured spinal cord. A recent clinical trial demonstrated improved motor function in domestic dogs with spinal injury following autologous OEC transplantation. Their utility in canines offers promise for human translation, as dogs are comparable to humans in terms of clinical management and genetic/environmental variation. Moreover, the autologous, minimally invasive derivation of OECs makes them viable for human spinal injury investigation. Genetic engineering of transplant populations may augment their therapeutic potential, but relies heavily on viral methods which have several drawbacks for clinical translation. We present here the first proof that magnetic particles deployed with applied magnetic fields and advanced DNA minicircle vectors can safely bioengineer OECs to secrete a key neurotrophic factor, with an efficiency approaching that of viral vectors. We suggest that our alternative approach offers high translational potential for the delivery of augmented clinical cell therapies.

Highlights

Spinal cord injury (SCI) can result in paralysis and reduction in patient quality of life, with high associated healthcare costs.[1]
We have previously shown that iron oxide magnetic particle (MP) vectors deployed with applied magnetic fields (‘magnetofection’) can safely engineer major rodent neural transplant populations including neural stem cells (NSCs) and oligodendrocyte precursor cells (OPCs).[21,22,23]
We demonstrate for the first time that non-viral MP based platforms in conjunction with magnetofection technology can safely and efficiently engineer canine olfactory mucosal cell (cOMC) populations, previously derived clinically for transplantation into dogs with SCI

Summary

Introduction

Spinal cord injury (SCI) can result in paralysis and reduction in patient quality of life, with high associated healthcare costs.[1]. In line with particle uptake, application of oscillating magnetic fields significantly enhanced transfection over the no field condition but with no further improvements over the static field (Fig. 1F).

Results

Conclusion