Biomedical subjects

F Solaiman

Publications and source records attributed to F Solaiman.

4 recordsLinked to original sources

PubMed2000

Modular retro-vectors for transgenic and therapeutic use.

Retroviruses have been used for many years as vectors for human gene therapy as well as for making transgenic animals. However, the efficient insertion of genes by retroviruses is often complicated by transcriptional inactivation of the retroviral long terminal repeats (LTRs) and by the production of replication-competent retroviruses (RCR). Solutions to these and other difficulties are being found in modular vectors, in which the desirable features of different vector systems are combined. Examples of synergistic vectors include virosomes (liposome/virus delivery), adeno-retro vectors, and MLV/VL30 chimeras. As gene delivery systems become increasingly complex, methodology is also needed for precise assembly of modular vectors. Gene self-assembly (GENSA) technology permits seamless vector construction and simultaneous, multifragment assembly.

Animals↗

PubMed2000

Fusogenic effects of murine retroviruses and cationic enhancers of transduction.

The maturation of retrovirus particles involves proteolytic cleavage of the envelope glycoprotein transmembrane component, resulting in conversion of the virus particle to a fusogenic or infectious state. Susceptible murine cells exposed to virus-containing supernatants from ecotropic retroviral helper cells occasionally fused to neighboring cells, resulting in syncytia (giant cells with multiple nuclei). Polycationic molecules dramatically enhanced the effect, leading to widespread cell death. The degree of cell fusion was dependent upon the retroviral envelope subtype (ecotropic-->amphotropic, gibbon ape leukemia virus was negative) as well as on the polycationic reagent used (G9 dendrimer-->Lipofectamine-->polybrene). Cell fusion effects were not mediated by the retroviral vector backbone, because virus-containing supernatants from helper cells (without vector) and vector producer cells had a similar effect. Human target cells were not fused by any type of murine retrovirus; in addition, amphotropic virus from human helper cells was not fusogenic toward murine cells. Thus, fusogenic effects were important during the propagation of vectors using murine helper cells but were not a significant factor during the transduction of human cells.

3T3 Cells↗

PubMed1997

Biosynthetic retrovectoring systems for gene therapy.

Chemical and physical methods of introducing genes into cells (transfection) are being combined with viral transduction as one possible approach toward overcoming the shortcomings of current gene transfer methods. Although several different strategies are being developed worldwide, this article focuses on modification of retroviral vectoring systems. One goal of this work is to combine the safety and ease of transfection methods with the permanency that is presently achieved only by integrating viruses. Work with retrotransposon pseudotypes, synthetic retrovectors, and liposomal delivery of retrovirus vectors is discussed.

Animals↗

PubMed1996

Virosomes: cationic liposomes enhance retroviral transduction.

Retrovirus-derived vectors are overwhelmingly preferred over other methods for ex vivo gene therapy because they provide permanent integration of foreign genes into cellular DNA. In comparison, cationic lipids mediate efficent gene transfer, but expression is transient. When we combined cationic lipids with retrovirus particles we obtained a significant enhancement of transduction efficiency, depending upon the type of lipid formulation and the dose used. The relative effectiveness of these cytofectins was: DOSPA:DOPE > DOTMA:DOPE > DOTAP, resulting in 60-, 37-, and 5-fold increases in transduction efficiency, respectively, at optimum dosage. The effect of polycationic DOSPA:DOPE was dependent upon the viral envelope glycoprotein, was attainable by lipid treatment of either cells or virus particles, was not enhanced by the addition of polybrene, and was inhibited by chloroquine. These results strongly suggested that DOSPA:DOPE act primarily by modulation of charge associated with the viral envelope and cell membrane, enhancing retroviral transduction, rather than by providing an alternative pathway of transfection. DOSPA:DOPE is useful for improving the efficiency of gene transfer as well as the sensitivity with which retroviruses can be detected in biological fluids.

3T3 Cells↗