Advancements in Non Viral Gene Therapy for Hemophilia

Bradley S Fletcher

doi:10.4172/2157-7412.s1-002

Abstract

Over the last 10-15 years, significant advances in vector design and delivery techniques have facilitated the development of nonviral approaches for the treatment of hemophilia. Despite these advancements, there remain several obstacles preventing the successful application of these approaches in larger mammals such as dogs and humans. This review covers nonviral gene therapy approaches using both in vivo gene delivery and ex vivo gene transfer. Plasmid-based approaches, as well as integrating transposons are examined for efficacy, risks and limitations. Results are presented on the only human clinical trial in hemophilia that utilized nonviral approaches.

Highlights

Hemophilia is a disorder of the blood coagulation cascade caused by deficiencies in Factor VIII (FVIII, hemophilia A) or Factor IX (FIX, hemophilia B)
This review focuses on recent advancements in nonviral gene delivery and the obstacles that remain preventing clinical use
Advances have been made in enhancing gene expression over time and basic insights have been made into how expression is lost

Summary

Introduction

Hemophilia is a disorder of the blood coagulation cascade caused by deficiencies in Factor VIII (FVIII, hemophilia A) or Factor IX (FIX, hemophilia B). There are a number of excellent reviews that cover current advances in the genetic treatment of hemophilia [13] Many of these reviews emphasize viral methods of gene delivery, which are effective and currently being evaluated in clinical trials. Nonviral gene delivery methods are less immunogenic as they contain no viral protein antigens that may activate the immune system. Nonviral gene delivery methods are less likely to cause insertional mutagenesis providing increased safety; this increase in safety is dependent on the type of vector used. The immunological effects of different nonviral gene delivery methods and the development of inhibitory antibodies are beyond the scope of this review, yet are another important facet of gene therapy for hemophilia. Regardless of the choice of nucleic acid, chemical or physical methods are required for efficient gene delivery

Chemical methods

Physical methods

Concluding Remarks