Synthetic mammalian retrotransposon gene

C04212: Synthetic mammalian retrotransposon gene

Value Proposition:


• Synthetic retrotransposable element that can integrate into the genome
• Exhibits a higher level of expression relative to natural L1 retrotransposon gene
• A new method for delivering desired DNA to humans and other mammals, including gene therapies
• Improves gene discovery methodology and other genetic applications in mammals
• Method for discovering potential “anticancer” tumor suppressor genes, or a biologically active fragments in cells

Technical Details:

BACKGROUND

Retrotransposons are mobile DNA elements that replicate and insert themselves into the genomes of their hosts in a process called retrotransposition. They are naturally occurring elements found in the cells of all eukaryotes. Long interspersed repetitive elements 1 (L1), are retrotransposons that constitute a large fraction of the mammalian genome and contain two open reading frames, ORF1 and ORF2, that code for an RNA-binding protein and a protein with endonuclease and reverse transcriptase activities. The ORF2 protein, encoded by ORF2 gene, is essential for retrotransposition activity; however, transcription through the L1 open reading frames (ORF1 and ORF2) is currently ineffective owing to an elongation defect. There is an unmet need for improving L1 transposition frequency in mammalian cells. TECHNOLOGY Researchers at Johns Hopkins University have developed a synthetic ORF2 gene to bypass the transcriptional defect and to improve the transposition levels 100-fold more efficiently than native L1 retrotransposon. They have synthesized a new L1 open reading frame, altering 24% of the nucleic acid sequence without changing the protein, and enabled a steady-state L1 RNA and its protein. The synthetic ORF2 gene is approximately 3800 base pairs long and was designed to optimize ORF2 gene expression utilizing “human-associated codons” found in highly expressed mammalian genes.

Looking for Partners:

This invention provides: 1) A vastly improved genetic analysis system for gene discovery in mammals 2) A method of discovering potential “anticancer” tumor suppressor genes 3) A novel method for delivering DNA to humans and other mammals, including gene therapy

Publications/Associated Cases:

Moran et al. 1996 “High frequency retrotransposition in cultured mammalian cells”. Cell 87, 917-927. and Han, J. S., & Boeke, J. D. (2004). A highly active synthetic mammalian retrotransposon. Nature, 429(6989), 314-318.