Femtosecond infrared laser - An efficient and safe in vivo gene delivery system for prolonged expression

Evelyne Zeira, Alexandra Manevitch, Artium Khatchatouriants, Orit Pappo, Esti Hyam, Merav Darash-Yahana, Einat Tavor, Alik Honigman, Aaron Lewis, Eithan Galun*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

125 Scopus citations


The major advantages of "naked DNA gene therapy" are its simplicity and a low or negligible immune response. Gene delivery by DNA electroporation (EP) involves injection of DNA and the application of a brief electric pulse to enhance cellular permeability. Although EP is an efficient gene transduction technique in rodents, it requires much higher voltages (>500 V) in larger animals, and hence, in practice it would be hazardous for human patients, as it would cause serious tissue damage. To overcome the obstacles associated with EP-mediated gene delivery in vivo, we developed a new method of gene transduction that uses laser energy. The femtosecond infrared titanium sapphire laser beam was developed specifically for enhancing in vivo gene delivery without risks of tissue damage. System optimization revealed that injection of 10 μg naked DNA into the tibial muscle of mice followed by application of the laser beam for 5 s, focused to 2 mm depth upon an area of 95 × 95 μm2, resulted in the highest intensity and duration of gene expression with no histological or biochemical evidence of muscle damage. We assessed the potential clinical application of LBGT technology by using it to transfer the murine erythropoietin (mEpo) gene into mice. LBGT-mediated mEpo gene delivery resulted in elevated (>22%) hematocrit levels that were sustained for 8 weeks. Gene expression following LBGT was detected for > 100 days. Hence, LBGT is a simple, safe, effective, and reproducible method for therapeutic gene delivery with significant clinical potential.

Original languageAmerican English
Pages (from-to)342-350
Number of pages9
JournalMolecular Therapy
Issue number2
StatePublished - 1 Aug 2003
Externally publishedYes

Bibliographical note

Funding Information:
We thank Dina Ben-Yehuda for her scientific support. This study was supported by a grant from the Israeli Ministry of Science, the San-Francisco Jewish Federation, the Blum Foundation, and the Sylvia and Martin Snow Charitable Foundation.


  • Electroporation
  • Gene expression in vivo
  • Gene therapy
  • Naked DNA
  • Nonviral vectors


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