Design of non-viral vector with improved regulatory features towards therapeutic application.

Huang Huang

doi:10.6026/97320630016307

Abstract

Viral vectors based gene therapy is often compromised by adverse immunological reactions raising safety concerns. Hence, improved design and development of non-viral vectors with strong regulatory regions is desired. We describe the design of a non-viral mammalian expression vector in which the primary transgene (a truncated dystrophin gene linked with Duchenne muscular dystrophy (DMD)) named microdystrophin delR4-R23/delCT (MD1) is under the transcriptional control of elements of desmin locus control region (DES-LCR). The designed vector, named as DES-LCR/MD1-EGFP, was constructed by cloning two fragments into the pBluescript backbone. Fragment 1 contains DES-LCR enhancer and DES-LCR promoter region while fragment 2 contains MD1 transgene and reporter EGFP (enhanced green fluorescent protein) gene separated by linker P2A (2A peptide). This vector design provides a framework for strong regulation with non-viral features. This design forms the foundation for application in conditions linked to multisystem diseases.

Highlights

Applications of gene therapy are tremendous and offers hope to treat genetic diseases at large
Non-viral vectors have been ignored in the past but they certainly represent the long-term future of gene therapy owing to their increased safety
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 [13]

Summary

Introduction

Applications of gene therapy are tremendous and offers hope to treat genetic diseases at large. Success of gene therapy lies on the design, development and delivery of vectors, which can be of viral and non-viral types. Viral and non-viral gene therapy vectors, have applications in preclinical and clinical settings. Viral vectors have emerged as effective gene therapy vehicles for clinical gene therapy [1], safety has been an issue on use of viral vectors since they may generate strong immune response [2]. Non-viral vectors have been ignored in the past but they certainly represent the long-term future of gene therapy owing to their increased safety.

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Conclusion