Bioengineered human skin: working the bugs out.

commentary equal, or greater, clinical relevance. 5 Thus far, a majority of therapeutic agents proposed for treatment of neurodegenerative disease are secreted trophic factors such as insulin-like growth factor 1 and glial cell line–derived neurotrophic factor. 29 Because most trophic factors are typically secreted by glia, it is easy to envision that rAAV-mediated overexpres-sion of trophic factors in these supporting cells would result in significant improvement of cell rescue, similar to or better than that seen when neurons themselves have been targeted. Although the neuronal transduction in the adult brain was limited in scope in the Foust et al. study, 5 the ubiquitous astrocytic transduction holds similar promise to that of astrocytic infection of the spinal cord. Trophic factors have been implicated as potential therapeutic agents aimed at slowing disease progression in neurodegenerative diseases such as Parkinson's disease. In the case of disorders that require more targeted delivery such as Parkinson's disease, the use of i.v. AAV9 might still be advantageous if tissue-specific promoters are included in the therapeutic construct, as pointed out correctly by Foust et al. 5 Although brain neurosur-gery is relatively safe, systemic delivery across the BBB remains an even safer alternative to direct CNS injections. Going forward, widespread protein expression in the CNS via the use of rAAV9 needs a proof of principle in a rodent model of a neurodegenerative disorder that can be treated with ectopic gene expression in astro-cytes. Moreover, replication of these results in other laboratories as well as in larger species will also constitute the next important hurdle for the method described by Foust et al. Use of adeno-associated virus as a mammalian DNA cloning vector: transduction of neomycin resistance into mammalian tissue culture cells. Neonatal intraperitoneal or intravenous injections of recombinant adeno-associated virus type 8 transduce dorsal root ganglia and lower motor neurons. (2006). Single amino acid changes can influence titer, heparin binding, and tissue tropism in different adeno-associated virus serotypes. and alpha2,6 N-linked sialic acids facilitate efficient binding and transduction by adeno-associated virus types 1 and 6. Adeno-associated virus type 2 contains an integrin alpha5beta1 binding domain essential for viral cell entry. A et al. (2002).The atomic structure of adeno-associated virus (AAV-2), a vector for human gene therapy. Structure of adeno-associated virus serotype 8, a gene therapy vector. and selection of shuffled AAV genomes: a new strategy for producing targeted biological nanoparticles. injection of adeno-associated virus type 1 (AAV1) in …