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PMID: 8289369 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A small and efficient dimerization/packaging signal of rat VL30 RNA and its use in murine leukemia virus-VL30-derived vectors for gene transfer.

Journal of virology ·Vol. 68 ·No. 2 ·1994-02-00 ·Pages 661-7

Torrent C, Gabus C, Darlix JL

Abstract

Retroviral genomes consist of two identical RNA molecules associated at their 5' ends by the dimer linkage structure located in the packaging element (Psi or E) necessary for RNA dimerization in vitro and packaging in vivo. In murine leukemia virus (MLV)-derived vectors designed for gene transfer, the Psi + sequence of 600 nucleotides directs the packaging of recombinant RNAs into MLV virions produced by helper cells. By using in vitro RNA dimerization as a screening system, a sequence of rat VL30 RNA located next to the 5' end of the Harvey mouse sarcoma virus genome and as small as 67 nucleotides was found to form stable dimeric RNA. In addition, a purine-rich sequence located at the 5' end of this VL30 RNA seems to be critical for RNA dimerization. When this VL30 element was extended by 107 nucleotides at its 3' end and inserted into an MLV-derived vector lacking MLV Psi +, it directed the efficient encapsidation of recombinant RNAs into MLV virions. Because this VL30 packaging signal is smaller and more efficient in packaging recombinant RNAs than the MLV Psi + and does not contain gag or glyco-gag coding sequences, its use in MLV-derived vectors should render even more unlikely recombinations which could generate replication-competent viruses. Therefore, utilization of the rat VL30 packaging sequence should improve the biological safety of MLV vectors for human gene transfer.

MeSH Terms
Animals Base Composition Base Sequence DNA Mutational Analysis Defective Viruses/genetics Gene Transfer Techniques Genetic Vectors/genetics Harvey murine sarcoma virus/genetics Molecular Sequence Data Moloney murine leukemia virus/genetics,growth & development Nucleic Acid Conformation RNA, Double-Stranded/genetics RNA, Viral/genetics Rats Recombination, Genetic Regulatory Sequences, Nucleic Acid/genetics Virus Replication
Chemicals
RNA, Double-Stranded RNA, Viral
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Torrent C
LaboRetro Institut National de la Santé et de la Recherche Médicale, Ecole Normale Supérieure de Lyon, France.
Gabus C
Darlix J L
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.68.2.661-667.1994
Published
1994-02-00
Pages
661-7
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC236500
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.68.2.661-667.1994 PMC Full Text View journal details
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