MuLV-based vectors pseudotyped with truncated HIV glycoproteins mediate specific gene transfer in CD4+ peripheral blood lymphocytes

Lodge, Robert; Subbramanian, RA; Forget, J; Lemay, Guy; Ea, Cohen

doi:10.1038/sj.gt.3300646

Cited by 18 publications

(11 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Retroviruses, for example, have been modified by pseudotyping with human immunodeficiency virus envelope proteins [94,95] or by substituting env domains with antibody fragments [96]. The specificity of adenoviral vectors was modified by coupling ligands for target-specific receptors to anti-fiber [97] or anti-knob [98] antibodies or including receptorbinding domains into the fiber proteins [99].…”

Section: Future Perspectivesmentioning

confidence: 99%

Gene therapy and gastrointestinal cancer: concepts and clinical facts

Hauses¹,

Schackert²

1999

Langenbeck's Arch Surg

View full text Add to dashboard Cite

Data on 22 clinical trials on malignancies of the gastrointestinal tract are available. They utilize a variety of gene-delivery methods and target cell populations, and there is considerable variety among their strategies. Gene transfer is performed by injection of naked plasmid DNA and by use of DNA-liposome complexes and viral vectors. In some cases, the gene transfer is carried out ex vivo and the patients receive genetically modified cells, whereas other approaches deliver the vector to the target cell population in vivo. The theoretical concepts of gene therapy can be divided into three groups. One approach makes use of suicide genes comprising bacterial or viral genes that convert a nontoxic prodrug into a highly cytotoxic chemotherapeutic agent at the tumor site. This approach aims at higher therapeutic specificity and fewer side effects than with the systemic delivery of cytotoxic agents. The second strategy makes an attempt to invoke the immune system to destroy malignant cells. Different strategies, such as immunization with genetically modified tumor cells or transfer of new genes to T cells, are considered to have clinical benefits. The major advantage of these immunotherapeutic approaches is the systemic effect both on the primary tumor and on metastases. The third strategy evolved from the insight that cancer is a genetic disease caused by activation of oncogenes or inactivation of tumor-suppressor genes. Compensation of genetic defects by the downregulation of activated oncogenes or the restoration of tumor-suppressor-gene functions may be able to revert the malignant phenotype of cancer cells. Of the 22 gene-therapy trials, 17 trials focus on immunotherapy. Only two trials make use of suicide genes and, in three trials, a functional copy of the p53 tumor-suppressor gene was reintroduced into malignant cells. Modalities for gene transfer and the strategies underlying gene therapy will be discussed in the context of gastrointestinal malignancies and the potential benefits for patients.

show abstract

Section: Future Perspectivesmentioning

confidence: 99%

Gene therapy and gastrointestinal cancer: concepts and clinical facts

Hauses¹,

Schackert²

1999

Langenbeck's Arch Surg

View full text Add to dashboard Cite

show abstract

“…For example, although the glycoprotein of the Mokola virus, a neurotropic lyssavirus, efficiently pseudotypes HIV-1 vectors [12], the pseudotyped vectors do not reproduce the specific neurotropism of the parental virus [11]. Nevertheless, even though the only case of a viral glycoprotein directing virus infection to a specific cell type is that of HIV-1 [38,39], several studies have shown that the transduction efficiency of a given target cell type is directly dependent on the type of glycoprotein used to coat retroviral vectors. For instance, the use of surface glycoproteins derived from viruses that cause lung infection and infect via the airway epithelia, like Ebola virus or influenza virus, may prove useful for gene therapy of the human airway [17].…”

Section: Properties Of Lenti-vectors Pseudotyped With Heterologous Glmentioning

confidence: 99%

Surface-engineering of lentiviral vectors

Verhoeyen

Cosset

2004

J. Gene Med.

View full text Add to dashboard Cite

SummaryVectors derived from retroviridae offer particularly flexible properties in gene transfer applications given the numerous possible associations of various viral surface glycoproteins (determining cell tropism) with different types of retroviral cores (determining genome replication and integration). Lentiviral vectors should be preferred gene delivery vehicles over vectors derived from onco-retroviruses such as murine leukemia viruses (MLVs) that cannot transduce non-proliferating target cells. Generating lentiviral vectors pseudotyped with different viral glycoproteins (GPs) may modulate the physicochemical properties of the vectors, their interaction with the host immune system and their host range. There are however important gene transfer restrictions to some non-proliferative tissues or cell types and recent studies have shown that progenitor hematopoietic stem cells in G 0 , nonactivated primary blood lymphocytes or monocytes were not transducible by lentiviral vectors. Moreover, lentiviral vectors that have the capacity to deliver transgenes into specific tissues are expected to be of great value for various gene transfer applications in vivo. Several innovative approaches have been explored to overcome such problems that have given rise to novel concepts in the field and have provided promising results in preliminary evaluations in vivo. Here we review the different approaches explored to upgrade lentiviral vectors, aiming at developing vectors suitable for in vivo gene delivery.

show abstract

“…These vectors are, therefore, widely used to deliver anti-HIV genes. Several retroviral vectors, including MLV-based vectors, can allow for therapeutic gene delivery into PBLs (177,178); however human HSCs seem to be difficult to transduce because they are difficult to isolate and are quiescent (179). Ex vivo delivery of the therapeutic gene into pluripotent HSCs via a retroviral vector requires that the stem cell be active, dividing, and not differentiating (179).…”

Section: Gene Delivery and Expressionmentioning

confidence: 99%