Lentiviral vectors: optimization of packaging, transduction and gene expression

Abstract

SummaryGene transfer vectors based on retroviruses including oncogenic retroviruses and lentiviruses provide effective means for the delivery, integration and expression of exogenous genes in mammalian cells. Lentiviral (LV) vectors provide attractive gene delivery vehicles in the context of non-dividing cells. This review summarizes the different optimized LV genetic systems that have been developed to date. In all cases, the production of LV-derived vectors consists of a genetically split gene expression design. The viral elements that are specifically required are (i) the LV packaging helper proteins consisting of at least the gag-pol genes, (ii) the LV transfer vector RNA containing the transgene expression cassette, and (iii) an heterologous glycoprotein. While the genetic requirements and performances of the two former viral elements will be treated herein, the latter element relative to the envelope pseudotyping of LV vectors will not be further described (cf. review by Cosset in this issue).

Gene therapy to inhibit xenoantibody production using lentiviral vectors in non-human primates

“…[33][34][35][36][37] We elected to use SIVderived lentiviral vectors for this study based on reports that they are more efficient for transduction of simian stem cells. 19,20,[38][39][40] Our results using SIV-based aGT constructs are consistent with those findings.…”

Intracellular trafficking of retroviral vectors: obstacles and advances

“…Since initial work with simple retroviruses like MLV to develop retroviral vectors, numerous vector systems based on simple and complex retroviruses now exist with various features, advantages and disadvantages too abundant to review here (discussed in Cockrell and Kafri, 6 Pages and Bru 7 and Delenda 13 ). However, their general attributes remain the same.…”

“…Although in practice, recombination between vector component/s or with endogenous retroviruses can generate undesirable replication-competent retrovirus. 6,7,13 To avoid such deleterious recombination, all unnecessary retroviral sequence is deleted from the packaging, envelope and vector constructs. By deleting nonessential sequence from the transgene vector, large transgenes can also be packaged.…”

Analysis of human immunodeficiency virus type 1 vector cis- and trans-acting elements production by means of Semliki Forest virus

“…1,2 Indeed, many potential target cells for gene transfer include neurons, myocytes, hepatocytes and hematopoietic stem cells, and many efforts have been carried out to deliver transgene into these tissues, both in vitro and in vivo. [3][4][5] Extensive studies have been focused over the years on the human immunodeficiency virus type 1 (HIV-1)-based vector, which currently represents the vector of choice for many basic and applied research investigations, 6 and recently it has been approved for human clinical studies. 7 Recombinant lentiviral particle production is obtained by transiently expressing the viral structural components along with the transfer vector 1 or, to a lesser degree, by the use of stable vector-producing cell lines.…”