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A synthetic snRNA m3G-CAP enhances nuclear delivery of exogenous proteins and nucleic acids.


ABSTRACT: Accessing the nucleus through the surrounding membrane poses one of the major obstacles for therapeutic molecules large enough to be excluded due to nuclear pore size limits. In some therapeutic applications the large size of some nucleic acids, like plasmid DNA, hampers their access to the nuclear compartment. However, also for small oligonucleotides, achieving higher nuclear concentrations could be of great benefit. We report on the synthesis and possible applications of a natural RNA 5'-end nuclear localization signal composed of a 2,2,7-trimethylguanosine cap (m(3)G-CAP). The cap is found in the small nuclear RNAs that are constitutive part of the small nuclear ribonucleoprotein complexes involved in nuclear splicing. We demonstrate the use of the m(3)G signal as an adaptor that can be attached to different oligonucleotides, thereby conferring nuclear targeting capabilities with capacity to transport large-size cargo molecules. The synthetic capping of oligos interfering with splicing may have immediate clinical applications.

SUBMITTER: Moreno PM 

PROVIDER: S-EPMC2665231 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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A synthetic snRNA m3G-CAP enhances nuclear delivery of exogenous proteins and nucleic acids.

Moreno Pedro M D PM   Wenska Malgorzata M   Lundin Karin E KE   Wrange Orjan O   Strömberg Roger R   Smith C I Edvard CI  

Nucleic acids research 20090210 6


Accessing the nucleus through the surrounding membrane poses one of the major obstacles for therapeutic molecules large enough to be excluded due to nuclear pore size limits. In some therapeutic applications the large size of some nucleic acids, like plasmid DNA, hampers their access to the nuclear compartment. However, also for small oligonucleotides, achieving higher nuclear concentrations could be of great benefit. We report on the synthesis and possible applications of a natural RNA 5'-end n  ...[more]

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