title: Natural human gene correction by small extracellular genomic DNA fragments.
abstract: Classical gene targeting employs natural homologous recombination for a gene correction using a specially designed and artificially delivered DNA construct but the method is very inefficient. On the other hand, small DNA fragments in the form of tiny chromatin-like particles naturally present in blood plasma can spontaneously penetrate into human cells and cell nuclei. We hypothesized that these natural DNA nanoparticles with recombinagenic free ends might be effective agents for gene replacement therapy. We demonstrate that a mixture of small fragments of total human chromatin from non-mutant cells added to a culture medium without transfection agents efficiently repaired a 47 base pair deletion in the CASP3 gene in 30% of treated human MCF7 breast cancer cells, as shown by restoration of caspase-3 apoptotic function and CASP3 DNA and mRNA structure. Such an innate gene replacement mechanism might function naturally in an organism using its own apoptotic DNA fragments. This mechanism might enable human cancer cell phenotype normalization in the presence of excess normal cells.
authors: Panagenic International, Inc., Philadelphia, Pennsylvania, USA. yakubovl@yahoo.com
authors: Leonid A
authors: LA
authors: Yakubov
authors: Vladimir A
authors: VA
authors: Rogachev
authors: Anastasia C
authors: AC
authors: Likhacheva
authors: Sergei S
authors: SS
authors: Bogachev
authors: Tamara E
authors: TE
authors: Sebeleva
authors: Alexander G
authors: AG
authors: Shilov
authors: Sergei I
authors: SI
authors: Baiborodin
authors: Natalia A
authors: NA
authors: Petrova
authors: Ludmila V
authors: LV
authors: Mechetina
authors: Mikhail A
authors: MA
authors: Shurdov
authors: Eric
authors: E
authors: Wickstrom
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D004247:DNA / Q000096:biosynthesis / Q000235:genetics*; D053938:DNA Fragmentation / Q000187:drug effects; D004260:DNA Repair / Q000235:genetics; D045604:Extracellular Fluid / Q000502:physiology*; D005260:Female; D015894:Genome, Human / Q000502:physiology; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000008:administration & dosage; D012474:Salmon; D052416:Targeted Gene Repair / Q000379:methods*
chemical_list: D004247:DNA