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Results for “directed evolution”

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At least 1,783 records · Page 99Linked to original sources
PubMed1999

Improving enzymes for cancer gene therapy.

New techniques now make it feasible to tailor enzymes for cancer gene therapy. Novel enzymes with desired properties can be created and selected from vast libraries of mutants containing random substitutions within catalytic domains. In this review, we first consider genes for the ablation of tumors, namely, genes that have been mutated (or potentially can be mutated) to afford enhanced activation of prodrugs and increased sensitization of tumors to specific chemotherapeutic agents. We then consider genes that have been mutated to provide better protection of normal host tissues, such as bone marrow, against the toxicity of specific chemotherapeutic agents. Expression of the mutant enzyme could render sensitive tissues, such as bone marrow, more resistant to specific cytotoxic agents.

Bone Marrow↗
PubMed1999

Enzyme beauty.

Explore the source record for details and available documents.

Catalysis↗
PubMed2000

Breeding of retroviruses by DNA shuffling for improved stability and processing yields.

Manufacturing of retroviral vectors for gene therapy is complicated by the sensitivity of these viruses to stress forces during purification and concentration. To isolate viruses that are resistant to these manufacturing processes, we performed breeding of six ecotropic murine leukemia virus (MLV) strains by DNA shuffling. The envelope regions were shuffled to generate a recombinant library of 5 x 106 replication-competent retroviruses. This library was subjected to the concentration process three consecutive times, with amplification of the surviving viruses after each cycle. Several viral clones with greatly improved stabilities were isolated, with the best clone exhibiting no loss in titer under conditions that reduced the titers of the parental viruses by 30- to 100-fold. The envelopes of these resistant viruses differed in DNA and protein sequence, and all were complex chimeras derived from multiple parents. These studies demonstrate the utility of DNA shuffling in breeding viral strains with improved characteristics for gene therapy.

Animals↗
PubMed1993

Local cerebral blood flow measured by xenon-enhanced CT during cryogenic brain edema and intracranial hypertension in monkeys.

We developed a closed-skull model of freeze injury-induced brain edema, a model classically thought to produce vasogenic edema, and observed the natural course of changes in edema and blood flow using xenon-enhanced computed tomography (CT) in five rhesus monkeys before and for up to 6 h post insult. Intracranial pressure (ICP) gradually rose throughout the duration of the experiment. CT scans and CBF images permitted direct observation of the evolution of the lesion and revealed early ischemia in the periphery of the injury zone that progressed over time in association with edema. Frequency histogram analysis of local CBF (ICBF) demonstrated subtle but potentially important changes in distribution of ICBF between and within hemispheres at various times post insult. Changes in ICBF distribution were phasic and dissociated from increases in ICP in the latter stages of injury. The Xe/CT CBF method can be used to evaluate the effects of injury and therapy on CBF in this and other models of acute brain injury.

Animals↗
PubMed2005

Crossover from 'mesoscopic' to 'universal' phase for electron transmission in quantum dots.

The measurement of phase in coherent electron systems--that is, 'mesoscopic' systems such as quantum dots--can yield information about fundamental transport properties that is not readily apparent from conductance measurements. Phase measurements on relatively large quantum dots recently revealed that the phase evolution for electrons traversing the dots exhibits a 'universal' behaviour, independent of dot size, shape, and electron occupancy. Specifically, for quantum dots in the Coulomb blockade regime, the transmission phase increases monotonically by pi throughout each conductance peak; in the conductance valleys, the phase returns sharply to its starting value. The expected mesoscopic features in the phase evolution--related to the dot's shape, spin degeneracy or to exchange effects--have not been observed, and there is at present no satisfactory explanation for the observed universality in phase behaviour. Here we report the results of phase measurements on a series of small quantum dots, having occupancies of between only 1-20 electrons, where the phase behaviour for electron transmission should in principle be easier to interpret. In contrast to the universal behaviour observed thus far only in the larger dots, we see clear mesoscopic features in the phase measurements when the dot occupancy is less than approximately 10 electrons. As the occupancy increases, the manner of phase evolution changes and universal behaviour is recovered for some 14 electrons or more. The identification of a transition from the expected mesoscopic behaviour to universal phase evolution should help to direct and constrain theoretical models for the latter.

Journal Article↗