Polymerases evolved in nature to synthesize DNA and RNA, and they underlie the storage and flow of genetic information in all cells. The availability of these enzymes for use at the bench has driven a revolution in biotechnology and medicinal research; however, polymerases did not evolve to function efficiently under the conditions required for some applications and their high substrate fidelity precludes their use for most applications that involve modified substrates. To circumvent these limitations, researchers have turned to directed evolution to tailor the properties and/or substrate repertoire of polymerases for different applications, and several systems have been developed for this purpose. These systems draw on different methods of creating a pool of randomly mutated polymerases and are differentiated by the process used to isolate the most fit members. A variety of polymerases have been evolved, providing new or improved functionality, as well as interesting new insight into the factors governing activity.
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http://dx.doi.org/10.1016/j.febslet.2013.10.040 | DOI Listing |
Viruses
December 2024
Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Treatment options for viral infections are limited and viruses have proven adept at evolving resistance to many existing therapies, highlighting a significant vulnerability in our defenses. In response to this challenge, we explored the modulation of cellular RNA metabolic processes as an alternative paradigm to antiviral development. Previously, the small molecule 5342191 was identified as a potent inhibitor of HIV-1 replication by altering viral RNA accumulation at doses that minimally affect host gene expression.
View Article and Find Full Text PDFBiology (Basel)
December 2024
Division of Biochemistry, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, Sendai 981-8558, Japan.
We propose a hypothesis for the simultaneous emergence of bacteria, archaea, viruses, and mobile elements by sequential and concrete biochemical pathways. The emergence process can be considered analogous to crystallization, where genetic and biochemical systems stabilize as organisms evolve from their common ancestor, the LUCA, which was a non-free-living pool of single operon type genomes including double-stranded (ds) DNA at an ancient submarine alkaline vent. Each dsDNA operon was transcribed by different systems in σ, TFIIB, or TBP genomes.
View Article and Find Full Text PDFPLoS Negl Trop Dis
January 2025
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, United States of America.
Background: Machupo virus (MACV) is a New World mammarenavirus (hereafter referred to as "arenavirus") and the etiologic agent of Bolivian hemorrhagic fever (BHF). No vaccine or antiviral therapy exists for BHF, which causes up to 35% mortality in humans. New World arenaviruses evolve separately in different locations.
View Article and Find Full Text PDFDiagn Microbiol Infect Dis
January 2025
Division of Infectious Diseases, Naval Medical Center San Diego, 34800 Bob Wilson Drive, San Diego, CA, 92134, USA; Department of Medicine, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
Entamoeba histolytica infections range from asymptomatic intestinal amebiasis to more severe syndromes like invasive colitis or hepatic abscess. While diagnostic tests available for assessing these infections have evolved, the optimal use of newer diagnostics like enteric multiplex Polymerase Chain Reaction (PCR) panels has not been fully established. Here we describe the case of a 34-year-old male with an amebic liver abscess (ALA) that was diagnosed via multiplex Gastrointestinal (GI) PCR panel on formed stool and subsequently confirmed by testing liver abscess fluid (off-label) on the same multiplex GI PCR panel leading to rapid diagnosis and targeted treatment modification with excellent outcome.
View Article and Find Full Text PDFEur Urol Open Sci
January 2025
Merck & Co. Inc, Rahway, NJ, USA.
Background And Objective: Treatment landscape in advanced prostate cancer (PC) is evolving. There is limited understanding of the factors influencing decision-making for genetic/genomic testing and the barriers to recommending testing and treatment in international real-world clinical practice following the approval of poly-adenosine diphosphate-ribose polymerase inhibitors (PARPi) for metastatic castration-resistant PC (mCRPC). This work aims to assess genetic/genomic testing patterns and methods, including for homologous recombination repair mutation (HRRm), and treatment decisions among physicians caring for patients with PC across the USA, Europe, and Asia.
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