Non-Viral Vector Mediated Gene Delivery: the Outsider to Watch Out For in Gene Therapy

Abstract

Nucleic acids have considerable potential as therapeutic agents in the treatment of pathologies including genetic diseases, viral infections and cancer therapies. The major challenge for the use of nucleic acids in therapy lies in safely delivering these anionic macromolecules to their intended sites of action. The increasing use of viral vectors in Human Gene Therapy clinical trials has emphasized the potential of nucleic acid-based approaches to address the unmet needs of drug-based treatments. While viral vector-based Gene Therapy is on everyone's mind with recently approved Luxturna™, as well as other viral vector-based treatments under Fast Track Designation, it is key to remember that non-viral vectors present considerable advantages in terms of reliability, safety and costs for nucleic-acid based therapies. At Polyplus-transfection ® , we develop powerful non-viral vectors to safely deliver nucleic acids in vivo to target a wide range of tissues, through various routes of administrations. Of these reagents, in vivo-jetPEI ® and its highest quality grade cGMP in vivo-jetPEI ® are acknowledged as a non-viral vector of choice to deliver nucleic acids respectively in animal preclinical studies and in human clinical trials, notably for cancer and immunotherapy.

Anti-α-synuclein ASO delivered to monoamine neurons prevents α-synuclein accumulation in a Parkinson's disease-like mouse model and in monkeys

“… 66 , 67 , 68 , 69 Non-viral approaches are biologically safer and much less immunogenic that viral vectors. 70 , 71 Conversely, for non-viral oligonucleotides to be effective, they must achieve delivery to affected regions or cells at appropriate concentrations. Furthermore, they must be stable, therefore they require additional protection measures (end-blocking, base modification, etc.…”

Intracerebral Administration of a Ligand-ASO Conjugate Selectively Reduces α-Synuclein Accumulation in Monoamine Neurons of Double Mutant Human A30P*A53T*α-Synuclein Transgenic Mice

“…Alternatives to viral strategies are currently being developed based on non-viral oligonucleotides (siRNA, ASO, miRNA). Non-viral approaches are biologically safer and much less immunogenic than viral vectors [ 46 , 47 , 48 , 49 ]. Conversely, for non-viral oligonucleotides to be effective, they must achieve delivery to affected regions or cells at appropriate concentrations.…”

Content analysis of vitamins, dietary fibers and amino acids in a wide collection of barley (Hordeum vulgare L.) from Tibet, China

“…With viral vectors dominating cell and gene therapy, non-viral vectors sidestep the main concerns that come with using viruses: safety, immunogenicity and manufacturing limits (yield, scaling-up and costs) [ 13 ]. New generation of vectors with increased safety are desirable for gene therapy of constitutional disorders to achieve permanent genetic modification and stable expression of transgenes.…”