Subject: Life Sciences, Molecular Biology Keywords: sleeping Beauty transposon; bidirectional promoters; gene expression; gene therapy; synthetic biology; RPBSA; EF-1; LMP2/TAP1
Online: 28 August 2020 (11:35:53 CEST)
Promoter choice is an essential consideration for transgene expression in gene therapy. The expression of multiple genes requires ribosomal entry or skip sites, or the use of multiple promoters. Promoters systems comprised of two separate, divergent promoters may significantly increase the size of genetic cassettes intended for use in gene therapy. However, an alternative approach is to use a single, compact bidirectional promoter. We identified strong and stable bidirectional activity of the RPBSA synthetic promoter comprised of a fragment of the human Rpl13a promoter, together with additional intron / exon structures. The Rpl13a-based promoter drove long-term bidirectional activity of fluorescent proteins. Similar results were obtained for the EF1-α and LMP2/TAP1 promoters. However, in a lentiviral vector, the divergent bidirectional systems failed to produce sufficient titres to translate into an expression system for dual chimeric antigen receptors (CAR) expression. Although bidirectional promoters show excellent applicability to drive short RNA in Sleeping Beauty transposon systems, their possible use in the lentiviral applications requiring longer and more complex RNA, such as dual CAR cassettes, is limited.
ARTICLE | doi:10.20944/preprints202011.0164.v1
Subject: Social Sciences, Accounting Keywords: impact factor; scientific significance; heavy tails; sleeping beauties
Online: 3 November 2020 (15:02:52 CET)
This article is devoted to discussing the famous Impact factor citation suited to indicate the published scientific result's significance. Considering this problem based on the available statistical data, we demonstrate that: Impact factor follows a distribution having a heavy power tail that may lead to inconsistency in scientifically comparable journals' evaluation. Further, we remark that many papers recognized as sleeping and seemingly sleeping beauties are not considered when calculating. This makes the impact factor unsuitable in evaluating the original, groundbreaking discoveries and their consequences. Due to permanent changes in the composition of the underlying datasets, the impact factor can not be considered as a reliable indicator and to be used as a consistent evaluation metric. Overall, discussing all represented impact factor obstacles and other appropriate considerations, we conclude that the considered index can hardly be used as a reliable estimator of the publication's significance.