Adenoassociated Virus

Adeno-associated virus is a small, DNA-containing parvovirus that has been isolated from humans and other animal species.[1-4] Several serotypes of AAV have been isolated from humans and nonhuman primates.[1,4] Adeno-associated virus is defective and replicates only in host cell nuclei when certain functions are provided by a coinfecting helper adenovirus (Ad) or herpesvirus.1-1,2-1 The mechanism of the helper function is not clearly defined but only a limited set of adenovirus genes, E1, E2A, E4, and the VA RNA are required.[1] Adeno-associated virus has a broad host range but the efficiency of transduction with AAV vectors of different serotypes varies because of differences in cell receptors utilized for entry, cellular trafficking of AAV particles, and uncoating of the viral genome in the cell nucleus. For AAV to replicate, or to function as a gene delivery vehicle, the uncoated single-stranded DNA genome must be converted to a double-stranded molecule to permit transcription and gene expression. Adeno-associated virus infection of cultured cell lines in the absence of helper functions results in persistence of the viral genome as a latent provirus which exhibits a high preference for integration at a specific region on human chromosome 19, but the efficiency and specificity of this process are mediated by the AAV rep gene.[5] Adeno-associated virus vectors have no rep gene and do not integrate efficiently.1-1-1

Adeno-associated virus particles are stable to heat and withstand robust purification procedures. Each particle has a protein coat and contains one linear, single-stranded DNA genome, but equal numbers of AAV particles contain a strand of either ''plus'' or ''minus'' complementary sense, and both types of particle are equally infectious. The AAV2 DNA[1] has one copy of the 145-nucleotide-long inverted terminal repeat (ITR) at each end enclosing two open reading frames for the rep gene and cap gene, respectively. The ITR sequences provide cis-acting functions for replication and encapsi-dation. The family of four rep proteins, Rep78, Rep68, Rep52, and Rep40, and the family of the three capsid proteins, VP1, VP2, and VP3, provide trans-acting functions for replication and encapsidation. In the presence of a helper such as adenovirus[1,2] the AAV single-strand genome is converted to a duplex replicating form (RF) then amplified to a large pool of progeny RF molecules that are precursors to encapsidated progeny genomes. In a single growth cycle of several days, AAV may yield in excess of 100,000 particles per cell. This large burst size is important for high specific productivity in vector production.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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