Cell-specific Molecule and Method for Importing DNA into pulmonary epithelial cell nuclei (24002)
A short DNA sequence that can be placed into any gene therapy vector for efficient targeted expression in pulmonary epithelial cells. This invention has applications in the treatment of a number of pulmonary diseases and disorders such as cystic fibrosis, acute respiratory distress syndrome, and pulmonary fibrosis.Significance: This technology overcomes two of the immense difficulties in gene therapy: cell specific targeting, and gene transfer to non-dividing cells. Use of this sequence also has the significant advantage of increased control of protein expression.
Background: Traditional approaches in targeting gene transfer have included delivery at specific physical site and the use of cell specific promoters. Although these methods improve gene targeting, such methods do not overcome the difficulties of nuclear import. Using a human gene with transcriptional specificity to lung cells, a promoter sequence has been identified which demonstrates specific nuclear targeting to pulmonary epithelial cells. This sequence can be inserted into a variety of vectors and directs specificity through cell specific nuclear import. This specificity results in increased gene nuclear uptake and expression efficiency. Furthermore this technology ensures that genes can be targeted to non-dividing cells. Additionally, because the sequence is independent of the vector’s promoter, a variety of promoters can be employed to control the desired level of therapeutic expression.
Dr. Dean has previously demonstrated the success of this technique using a different targeting sequence. A portion of the smooth muscle gamma actin promoter gene, whose expression is limited to smooth muscle cells, was utilized to engineer reporter plasmids that expressed selectively in smooth muscle cells. Moreover when injected into the cytoplasm, these plasmids localize to the nucleus of smooth muscle cells, but remain cytoplasmic in fibroblasts and CV1 cells. (Vacik, J. et. al. Gene Therapy (1999) 6, 1006-1014) (US patent 6,130,207)
Status: A patent application has been filed and Northwestern University is interested in licensing this technology
Type of Offer: Licensing
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