Topic Introduction

Engineering the Surface Glycoproteins of Lentiviral Vectors for Targeted Gene Transfer

Adapted from Gene Transfer: Delivery and Expression of DNA and RNA (eds. Friedmann and Rossi). CSHL Press, Cold Spring Harbor, NY, USA, 2007.

INTRODUCTION

Vectors derived from retroviruses such as lentiviruses and oncoretroviruses are especially suitable tools for long-term gene transfer, because they allow stable integration of a transgene and its propagation in daughter cells. Lentiviral vectors are preferred over vectors derived from oncoretroviruses such as murine leukemia virus (MLV) vectors, because they can transduce nonproliferating target cells. Moreover, lentiviral vectors that can target tissues specifically will be valuable for various gene-transfer approaches in vivo. To achieve targeted gene transfer, two types of surface modifications have been made to lentiviral vectors: (1) heterologous viral glycoproteins have been incorporated to exploit the tropism of other viruses (this is called pseudotyping), and (2) heterologous polypeptides have been fused to viral glycoproteins to retarget the lentiviral particles to a cell of interest. This article provides an overview of innovative approaches to upgrade lentiviral vectors for tissue targeting.