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Omar B Alexander

Publications and source records attributed to Omar B Alexander.

3 recordsLinked to original sources
PubMed2006

Viral vector strategy for glial cell line-derived neurotrophic factor therapy for stroke.

Glial cell line-derived neurotrophic factor (GDNF) is a member of the transforming growth factor-beta superfamily. Over the last decade, GDNF has been shown to promote regenerative and restorative effects on dopaminergic neurons. Accumulating evidence also demonstrates that administration of GDNF to areas of ischemic brain injury limits cerebral infarction and reduces damage to motor functions in animal models of stroke. Neurotrophic factor and anti-apoptotic mechanisms, among others, have been proposed to underlie the therapeutic effects of GDNF. A major obstacle for GDNF therapy is the protein delivery to the brain, as well as its sustained bioavailability over time. Gene therapy and the use of viral vectors offer a technique for longevity of GDNF expression within the brain. In this review, we consider the risks and benefits of GDNF gene therapy as it relates to the treatment of stroke.

Animals↗
PubMed2003

A comparison of directed evolution approaches using the beta-glucuronidase model system.

Protein engineers can alter the properties of enzymes by directing their evolution in vitro. Many methods to generate molecular diversity and to identify improved clones have been developed, but experimental evolution remains as much an art as a science. We previously used DNA shuffling (sexual recombination) and a histochemical screen to direct the evolution of Escherichia coli beta-glucuronidase (GUS) variants with improved beta-galactosidase (BGAL) activity. Here, we employ the same model evolutionary system to test the efficiencies of several other techniques: recursive random mutagenesis (asexual), combinatorial cassette mutagenesis (high-frequency recombination) and a versatile high-throughput microplate screen. GUS variants with altered specificity evolved in each trial, but different combinations of mutagenesis and screening techniques effected the fixation of different beneficial mutations. The new microplate screen identified a broader set of mutations than the previously employed X-gal colony screen. Recursive random mutagenesis produced essentially asexual populations, within which beneficial mutations drove each other into extinction (clonal interference); DNA shuffling and combinatorial cassette mutagenesis led instead to the accumulation of beneficial mutations within a single allele. These results explain why recombinational approaches generally increase the efficiency of laboratory evolution.

Directed Molecular Evolution↗