Sindbis virus vectors for expression in animal cells

Current Opinion in Biotechnology

Volumn 7, Issue 5, 1996, Pages 531-535

  Huang, Henry V ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; NUCLEIC ACID; RNA; VACCINE;

ALPHA VIRUS; EXPRESSION VECTOR; GENE EXPRESSION; IMMUNIZATION; MOLECULAR CLONING; NONHUMAN; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN EXPRESSION; SHORT SURVEY; SINDBIS VIRUS; VACCINE PRODUCTION; VIRION; VIRUS GENOME;

ALPHAVIRUS; ANIMALIA; SINDBIS VIRUS;

EID: 0030272123     PISSN: 09581669     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0958-1669(96)80057-7     Document Type: Article

References (47)

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35. Olson KE, Higgs S, Gaines PJ, Powers AM, Davis BS, Kamrud KI, Carlson JO, Blair CD, Beaty BJ. Genetically engineered resistance to dengue-2 virus transmission in mosquitoes. of special interest Science. 272:1996;884-886 A SIN vector expressing an antisense RNA corresponding to the prM region of the dengue-2 genome was used to produce intracellular immunity to dengue-2 virus. Mosquitoes infected with the antisense-expressing vector were rendered nontransmitting, with no dengue-2 virus detectable in the saliva. Thus, an antisense inhibition approach seems to be effective for inhibiting growth of a flavivirus in the disease transmitting insect. This suggests that SIN vectors should be generally useful for testing the effectiveness of different approaches and specific gene products for obtaining intracellular immunity against any of a number of pathogens transmitted by mosquitoes.
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39. Jiang W, Venugopal K, Gould EA. Intracellular interference of tick-borne flavivirus infection by using a single-chain antibody fragment delivered by recombinant Sindbis virus. of special interest J Virol. 69:1995;1044-1049 A dsSIN vector was used to express and test the effectiveness of single chain antibodies for intracellular immunization. The antibody against a neutralizing epitope of louping ill virus, when expressed by the dsSIN vector, bound antigen and inhibited the growth of the virus. This is one of several papers reporting on different strategies for intracellular immunization (see also [34,35]) that exploit the ease of use, the good expression levels, and the wide host range of the SIN vectors.
40. Higgs S, Olson KE, Klimowski L, Powers AM, Carlson JO, Possee RD, Beaty BJ. Mosquito sensitivity to a scorpion neurotoxin expressed using an infectious Sindbis virus vector. of outstanding interest Insect Mol Biol. 4:1995;97-103 Mosquitoes that normally show only subtle effects after infection by wild-type SIN died within a few days after infection by SIN vectors expressing a scorpion toxin. Houseflies and a tick were unaffected. This paper shows the usefulness of SIN vectors in screening for agents that are specifically lethal to the disease-transmitting insect. As speculated in the main text, the SIN vectors may also be used to transmit the same lethal agent to mosquitoes when they bite a suitably engineered animal.
41. Ulmer JB, Donnelly JJ, Parker SE, Rhodes GH, Felgner PL, Dwarki VJ, Gromkowski SH, Deck RR, DeWitt CM, Friedman A, et al. Heterologous protection against influenza by injection of DNA encoding a viral protein. Science. 259:1993;1745-1749.
42. Driver DA, Latham EM, Polo JM, Belli BA, Banks TA, Chada S, Brumm D, Chang SMW, Mento SJ, Jolly DJ, Dubensky TW Jr. Layered amplification of gene expression with a DNA gene delivery system. of special interest Ann NY Acad Sci. 772:1995;261-264 Naked DNA plasmids that express the SIN vectors using RNA polymerase II-dependent promoters gave substantially higher expression levels than the reporter gene under direct control of the same pol II-dependent promoter. The duration of the expression was extended compared to that resulting from the injection of naked RNA, indicating the persistence of the DNA plasmids in the injected tissues. Clones that express the hepatitis B core or e proteins were able to induce the production of specific antibodies. Thus, SIN vectors may be useful for enhancing the expression levels for DNA-based nucleic immunization. See also [43].
43. Dubensky TW Jr, Driver DA, Polo JM, Belli BA, Latham EM, Ibanez CE, Chada S, Brumm D, Banks TA, Mento SJ, et al. Sindbis virus DNA-based expression vectors: utility for in vitro and in vivo gene transfer. of special interest J Virol. 70:1996;508-519 The RNA genomes of SIN vectors are usually transcribed in vitro for transfection into host cells. This paper, together with [42] (see also [10]), reports the construction of clones where the RNA genome of the replicon and helper vectors are transcribed from different pol II-dependent promoters in transformed cells. As expected, the expression level of the luciferase reporter gene is much enhanced over of the typical host transcription processes, because of the replication amplification of the SIN vector genomes. The naked DNA plasmids of the clones also expressed the reporter gene when injected into mouse muscles, thus demonstrating that the SIN vectors can be used even in the context of classical DNA-based nucleic acid immunization.
44. Minor PD. Regulatory issues in the use of DNA vaccines. Ann NY Acad Sci. 772:1995;170-177.
45. Johanning FW, Conry RM, LoBuglio AF, Wright M, Sumerel LA, Pike MJ, Curiel DT. A Sindbis virus mRNA polynucleotide vector achieves prolonged and high level heterologous gene expression in vivo. of outstanding interest Nucleic Acids Res. 23:1995;1495-1501 This paper raised the biosafety problem of the potential need to use nucleic acid immunization to immunize against oncoproteins. The authors instead proposed to use RNA vectors for these applications. They showed that the naked RNA of a SIN replicon vector expressing the luciferase reporter gene gave expression for up to 10 days after injection into mouse muscle. The expression level and persistence of expression was substantially better than that of nonreplicative mRNAs. The expression level is 10-fold lower than that of a DNA-based plasmid expression system when comparable amounts (50 μg) were injected, but, significantly, whereas DNA-based expression persisted to at least 28 days, expression by the SIN vector was no longer detectable at the same time point. This suggests that, in contrast to DNA-based systems, RNA-based nucleic acid immunization might not present potential biosafety problems associated with the persistence of the foreign DNA and its prolonged expression.
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