Altering the Tropism of Lentiviral Vectors through Pseudotyping

Abstract

The host range of retroviral vectors including lentiviral vectors can be expanded or altered by a process known as pseudotyping. Pseudotyped lentiviral vectors consist of vector particles bearing glycoproteins (GPs) derived from other enveloped viruses. Such particles possess the tropism of the virus from which the GP was derived. For example, to exploit the natural neural tropism of rabies virus, vectors designed to target the central nervous system have been pseudotyped using rabies virusderived GPs. Among the first and still most widely used GPs for pseudotyping lentiviral vectors is the vesicular stomatitis virus GP (VSV-G), due to the very broad tropism and stability of the resulting pseudotypes. Pseudotypes involving VSV-G have become effectively the standard for evaluating the efficiency of other pseudotypes. This review samples a few of the more prominent examples from the ever-expanding list of published lentiviral pseudotypes, noting comparisons made with pseudotypes involving VSV-G in terms of titer, viral particle stability, toxicity, and host-cell specificity. Particular attention is paid to publications of successfully targeting a specific organ or cell types.

Pseudotyping lentiviral vectors with the wild-type measles virus glycoproteins improves titer and selectivity

“…They can be pseudotyped with glycoproteins from other enveloped viruses, in some cases after the truncation of cytoplasmic tails that interfere with particle incorporation. 1,2 The glycoprotein G of vesicular stomatitis virus (VSV) has widely been used for pseudotyping. 3 Recently, we achieved pseudotyping of lentiviral vectors with the envelope proteins of a vaccine strain of measles virus (MV).…”

Visualization of targeted transduction by engineered lentiviral vectors

“…[5][6][7] Sometimes, to achieve a desirable therapeutic effect, the viral vectors must be capable of precisely delivering a gene of interest to specific cells without influencing non-target cells. [8][9][10] Many efforts have been made to develop such targeting viral vector systems mostly by altering the viral envelope glycoprotein. [11][12][13][14][15][16] Although certain envelope glycoproteins are structurally plastic enough to allow insertion of a new molecular recognition unit (such as peptide, single chain antibody, growth factor and so on) for targeting, this manipulation can adversely affect the delicate coupling interactions of the binding and fusion domains of glycoproteins, resulting in enveloped vectors with decreased infectivity to the target cells.…”

“…[11][12][13][14][15][16] Although certain envelope glycoproteins are structurally plastic enough to allow insertion of a new molecular recognition unit (such as peptide, single chain antibody, growth factor and so on) for targeting, this manipulation can adversely affect the delicate coupling interactions of the binding and fusion domains of glycoproteins, resulting in enveloped vectors with decreased infectivity to the target cells. 8,15,[17][18][19] We have previously developed an efficient method to target lentivirus-mediated gene transduction to a desired cell type. 10 Our engineering approach involved the incorporation of a targeting antibody and pH-dependent fusogenic protein as two distinct molecules on the lentiviral surface.…”

Library selection and directed evolution approaches to engineering targeted viral vectors

“…Pseudotyping, the packaging of vectors with any of a number of heterologous viral envelope proteins rather than the retroviral envelope, can offer the ability to change or extend cell tropism (Cronin et al, 2005). However, pseudotyping is still restricted to a relatively limited collection of viral envelope options.…”