Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector

Luigi Naldini, Ulrike Blomer, Fred H. Gage, Didier Trono, Inder M. Verma

Research output: Contribution to journalArticlepeer-review

Abstract

We describe the construction of a safe, replication-defective and efficient lentiviral vector suitable for in vivo gene delivery. The reverse transcription of the vector was found to be a rate-limiting step; therefore, promoting the reaction inside the vector particles before delivery significantly enhanced the efficiency of gene transfer. After injection into the brain of adult rats, sustained long-term expression of the transgene was obtained in the absence of detectable pathology. A high proportion of the neurons in the areas surrounding the injection sites of the vector expressed the transduced β-galactosidase gene. This pattern was invariant in animals sacrificed several months after a single administration of the vector. Transduction occurs by integration of the vector genome, as it was abolished by a single amino acid substitution in the catalytic site of the integrase protein incorporated in the vector. Development of clinically acceptable derivatives of the lentiviral vector may thus enable the sustained delivery of significant amounts of a therapeutic gene product in a wide variety of somatic tissues.

Original languageEnglish
Pages (from-to)11382-11388
Number of pages7
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number21
DOIs
Publication statusPublished - Oct 15 1996

ASJC Scopus subject areas

  • Genetics
  • General

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