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PubMed · 14261529

CIRCULATING DNA AS A POSSIBLE FACTOR IN ONCOGENESIS.

A BENDICH·T WILCZOK·E BORENFREUND
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Abstract

Infectious DNA from the tumor-inducing polyoma virus and pneumococcal-transforming DNA can be recovered from the blood of mice in biologically active form after intraperitoneal injection. Polyoma DNA appeared to undergo less inactivation than did transforming DNA. In light of these observations, the metastatic spread of cancer may possibly be favored by circulation of tumorigenic DNA in the blood stream.

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Administration, IntravenousAnimalsBiological TransportBloodCarcinogenesisCell Transformation, NeoplasticDNADNA, ViralInjections, IntraperitonealInjections, IntravenousMetabolismMiceNeoplasm MetastasisNeoplasmsPhosphorus IsotopesPolyomavirusRadiometryResearchTritiumBIOLOGICAL TRANSPORTBLOODDNA, VIRALEXPERIMENTAL LAB STUDYINJECTIONS, INTRAPERITONEALINJECTIONS, INTRAVENOUSMETABOLISMMICENEOPLASM ETIOLOGYNEOPLASM METASTASISPHOSPHORUS ISOTOPESPOLYOMA VIRUSRADIOMETRYTRITIUMJournal Article

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A BENDICH, T WILCZOK, E BORENFREUND. 1965-04-16. CIRCULATING DNA AS A POSSIBLE FACTOR IN ONCOGENESIS.. https://doi.org/10.1126/science.148.3668.374

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AAV capsid variants with brain-wide transgene expression and decreased liver targeting after intravenous delivery in mouse and marmoset.

Genetic intervention is increasingly being explored as a therapeutic option for debilitating disorders of the central nervous system. The safety and efficacy of gene therapies rely upon expressing a transgene in affected cells while minimizing off-target expression. Here we show organ-specific targeting of adeno-associated virus (AAV) capsids after intravenous delivery, which we achieved by employing a Cre-transgenic-based screening platform and sequential engineering of AAV-PHP.eB between the surface-exposed AA452 and AA460 of VP3. From this selection, we identified capsid variants that were enriched in the brain and targeted away from the liver in C57BL/6J mice. This tropism extends to marmoset (Callithrix jacchus), enabling robust, non-invasive gene delivery to the marmoset brain after intravenous administration. Notably, the capsids identified result in distinct transgene expression profiles within the brain, with one exhibiting high specificity to neurons. The ability to cross the blood-brain barrier with neuronal specificity in rodents and non-human primates enables new avenues for basic research and therapeutic possibilities unattainable with naturally occurring serotypes.

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