Improving therapeutic potential of non-viral minimized DNA vectors

Abstract

The tragic deaths of three patients in a recent AAV-based X-linked myotubular myopathy clinical trial highlight once again the pressing need for safe and reliable gene delivery vectors. Non-viral minimized DNA vectors offer one possible way to meet this need. Recent pre-clinical results with minimized DNA vectors have yielded promising outcomes in cancer therapy, stem cell therapy, stem cell reprograming, and other uses. Broad clinical use of these vectors, however, remains to be realized. Further advances in vector design and production are ongoing. An intriguing and promising potential development results from manipulation of the specific shape of non-viral minimized DNA vectors. By improving cellular uptake and biodistribution specificity, this approach could impact gene therapy, DNA nanotechnology, and personalized medicine.

Supercoiling and looping promote DNA base accessibility and coordination among distant sites

“…The minicircle system we developed to study supercoilingdependent structural changes has additional DNA nanotechnology applications (reviewed in 128 ), including for gene therapy [129][130][131][132] . DNA nanoparticles (specific shapes formed from annealed single strands of DNA) have been used for targeted drug delivery 133 , genome editing 134 , diagnostic imaging 135 , quantitative biosensing of biomarkers 136 , and many additional previously unanticipated applications 137 .…”

Therapeutic Effects and Repair Mechanism of HGF Gene-Transfected Mesenchymal Stem Cells on Injured Endometrium

“…To improve the effect of cell therapy, gene therapy with minicircle gene delivery vectors offers one possible way to meet this demand. The cumulative preclinical results with minicircle gene delivery vectors have yielded promising outcomes in stem cell therapy and stem cell reprograming [ 43 ]. Moreover, there are multiple clinical trials using mesenchymal stem cells, and several of them are phase III trials.…”

Improving cell and gene therapy safety and performance using next-generation Nanoplasmid vectors

“…Various investigators have subsequently identified that minicircle vectors are also superior to plasmid vectors when used in the production of AAV vectors (resulting in improved transducing unit titers, Table 1 ) or used as transposon vectors (resulting in increased transposition, Table 2 ), and CRISPR-Cas9 vectors (increased gene editing, Table 2 ). 50 …”