Nuclear Targeted DNA
- 详细技术说明
- Inventor: Kevin RicePharmaceutical Sciences and Experimental TherapeuticsMedicinal and Natural Products Chemistryhttp://pharmacy.uiowa.edu/rice
- *Abstract
-
Compositionsfor Targeting Non-viral Nucleic Acid Delivery
Targetingpeptides attached to plasmids are capable of directing the genetic material tosub-cellular locations within a cell.
Background
Exogenous plasmid DNA can be introduced into a cellvia viral and non-viral methods for gene therapy and laboratory studies. In thecases utilizing non-viral methodology, it has been difficult to target thegenetic material preferentially to the cell nucleus or other desiredsub-cellular location. Once the exogenous DNA entered the cells, it passivelyrelied on relatively non-specific mechanisms to recognize it as geneticmaterial and transport it to the nucleus during the next round of celldivision. If plasmids could be targeted specifically to desired sub-cellularorganelles, it could increase transfection efficiency and enable newtechnologies in research and clinic settings.
Technology
Researchers at the University of Iowa have developeda composition and method that provides for the targeting of non-viral vectorsto specific sub-cellular organelles within a host cell. This technology utilizesazidotetrafluorobenzylamide or related compounds at the N-terminus of asynthesized targeting peptide, which is able to co-opt endogenous cellmachinery to target its molecular cargo. When this peptide-hybrid compositionis exposed to 365nm light in the presence of plasmid DNA, it covalently bondsto the nucleic acid (while avoiding UV crosslinking of DNA) and positions thepeptide for efficient recognition by cell machinery. This technology can beused to incorporate nuclear localization sequences (NLS) such as SV40 large T NLS,M9 NLS, c-myc NLS, nucleoplasmin NLS, Xenopus N1 NLS, FGF3 NLS and PARP NLS, aswell as fusogenic peptide sequences, antimicrobial peptide sequences, etc. forsub-cellular targeting of nucleic acids. A photolabeling reaction which illustratesthe attachment of an NLS to a purine nucleoside is shown below.
Advantages
· SUB-CELLULAR TARGETING OF PLASMID.Non-viral plasmids can be specifically and efficiently targeted to sub-cellularlocations within the target cell through the use of peptide signals that havebeen demonstrated to target nascent cellular proteins.
· COVALENT ATTACHMENT OF TARGETINGSEQUENCE. Targeting sequences are bound to plasmids using a photocrosslinkingtechnology that creates a strong bond which is maintained during plasmidhandling and treatment.
PatentLink
UIRF has been awarded a patent for this technology(7,795,380).
http://www.google.com/patents?id=9R_WAAAAEBAJ&pg=PA46&lpg=PA46&dq=7,795,380&source=bl&ots=QYtwtKZG-j&sig=NdFsHnWnevixT8S9OzzQgo4-kJo&hl=en&sa=X&ei=Pn4iUNiQHOOsywG6zICICg&sqi=2&pjf=1&ved=0CDAQ6AEwAA#v=onepage&q=7%2C795%2C380&f=false
- *Licensing
- Shannon Sheehan, PhD, MBASenior Licensing Associate University of Iowa Research FoundationEmail: shannon-sheehan@uiowa.eduPhone: (319) 335-4605
- 国家/地区
- 美国
