scholarly journals Chemical Modification of Oligonucleotides: A Novel Approach Towards Gene Targeting

Mutagenesis ◽  
10.5772/50393 ◽  
2012 ◽  
Author(s):  
Hidetaka Torigoe ◽  
Takeshi Imanishi
Keyword(s):  
Chemical Modification ◽  
Gene Targeting ◽  
Novel Approach

scholarly journals Novel Approach in the Construction of Bioethanol-Producing Saccharomyces cerevisiae Hybrids

2019 ◽  
Vol 57 (1) ◽  
pp. 5-16 ◽  
Author(s):  
Anamarija Štafa ◽  
Andrea Pranklin ◽  
Ivan Krešimir Svetec ◽  
Božidar Šantek ◽  
Marina Svetec Miklenić ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Gene Targeting ◽  
Co2 Production ◽  
Production Test ◽  
Fermentation Inhibitors ◽  
Lignocellulosic Hydrolysates ◽  
Novel Approach ◽  
Ethanol Producer ◽  
High Ethanol ◽  
Selection Of

Bioethanol production from lignocellulosic hydrolysates requires a producer strain that tolerates both the presence of growth and fermentation inhibitors and high ethanol concentrations. Therefore, we constructed heterozygous intraspecies hybrid diploids of Saccharomyces cerevisiae by crossing two natural S. cerevisiae isolates, YIIc17_E5 and UWOPS87-2421, a good ethanol producer found in wine and a strain from the flower of the cactus Opuntia megacantha resistant to inhibitors found in lignocellulosic hydrolysates, respectively. Hybrids grew faster than parental strains in the absence and in the presence of acetic and levulinic acids and 2-furaldehyde, inhibitors frequently found in lignocellulosic hydrolysates, and the overexpression of YAP1 gene increased their survival. Furthermore, although originating from the same parental strains, hybrids displayed different fermentative potential in a CO2 production test, suggesting genetic variability that could be used for further selection of desirable traits. Therefore, our results suggest that the construction of intraspecies hybrids coupled with the use of genetic engineering techniques is a promising approach for improvement or development of new biotechnologically relevant strains of S. cerevisiae. Moreover, it was found that the success of gene targeting (gene targeting fidelity) in natural S. cerevisiae isolates (YIIc17_E5α and UWOPS87-2421α) was strikingly lower than in laboratory strains and the most frequent off-targeting event was targeted chromosome duplication.

A novel approach for enhancing the catalytic efficiency of a protease at low temperature: Reduction in substrate inhibition by chemical modification

2009 ◽  
Vol 103 (4) ◽  
pp. 676-686 ◽  
Author(s):  
Khawar Sohail Siddiqui ◽  
Don M. Parkin ◽  
Paul M. G. Curmi ◽  
Davide De Francisci ◽  
Anne Poljak ◽  
...  
Keyword(s):  
Low Temperature ◽  
Chemical Modification ◽  
Substrate Inhibition ◽  
Catalytic Efficiency ◽  
Temperature Reduction ◽  
Novel Approach ◽  
Low Temperature Reduction

scholarly journals NOVEL APPROACH TO MODEL BRAIN TUMOURS BY INDUCING LOCALLY RESTRICTED AND STEM CELL SELECTIVE GENE TARGETING

2014 ◽  
Vol 16 (suppl 3) ◽  
pp. iii7-iii7
Author(s):  
S. Brandner ◽  
A. Benedykcinska ◽  
N. Li ◽  
N. Henriquez
Keyword(s):  
Stem Cell ◽  
Gene Targeting ◽  
Brain Tumours ◽  
Novel Approach

scholarly journals Exploration of anti EFG1 locked nucleic acid gapmers to control Candida albicans filamentation

2021 ◽  
Vol 3 (12) ◽  
Author(s):  
Daniela Araújo ◽  
Dalila Mil-Homens ◽  
Per Trolle Jørgensen ◽  
Arsénio M. Fialho ◽  
Jesper Wengel ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nucleic Acid ◽  
Chemical Modification ◽  
Therapeutic Potential ◽  
Locked Nucleic Acid ◽  
Novel Approach ◽  
Candida Infections ◽  
In Vitro Performance

Introduction: Antisense oligonucleotides (ASOs) have been successfully utilized to silence gene expression for the treatment of many genetic human diseases, and particularly the locked nucleic acid (LNA) chemical modification is extensively used with this propose. However, LNA-modified ASOs have never been exploited for controlling virulence genes of Candida. EFG1is an important determinant of virulence that is involved in the switch from yeast to filamentous forms in C. albicans. Thus, our main goal was to explore LNA antisense gapmers for controlling EFG1gene expression and to block C. albicans filamentation. Methods: A set of five LNA-modified gapmers were designed with different chemical modifications (phosphorothioate backbone (PS) and/or palmitoyl-2’-amino-LNA) and ASO length. The in vitro performance of the different ASOs was evaluatedon their ability to control EFG1 gene expression, by qRT-PCR, and to reduce C. albicans’ filamentation, through filaments’ enumeration by microscopy. The in vivo therapeutic potential of ASOs was assessed using a G. mellonella model of infection, through a survival assay. Results: In vitro results showed that all ASOs were able to reduce the levels of EFG1gene expression, consequently reducing the levels of C. albicans filamentation around 50%. Interestingly, in vivo tests showed that the LNA-modified gapmer with PS backbone and palmitoyl-2’-amino-LNA was more effective at preventing G. mellonella infections. Conclusions: Undeniably, this work promotes the development of a novel approach for the treatment of Candida infections based on the delivery of ASOs coupled with LNA chemical modification.

Copper-dependent ATP7B up-regulation drives the resistance of TMEM16A-overexpressing head-and-neck cancer models to platinum toxicity

2019 ◽  
Vol 476 (24) ◽  
pp. 3705-3719 ◽  
Author(s):  
Avani Vyas ◽  
Umamaheswar Duvvuri ◽  
Kirill Kiselyov
Keyword(s):  
Oxidative Stress ◽  
Head And Neck ◽  
Transcriptional Activation ◽  
Platinum Resistance ◽  
Mrna Levels ◽  
Strong Positive Correlation ◽  
Platinum Compounds ◽  
Copper Chelation ◽  
Novel Approach ◽  
Cancer Models

Platinum-containing drugs such as cisplatin and carboplatin are routinely used for the treatment of many solid tumors including squamous cell carcinoma of the head and neck (SCCHN). However, SCCHN resistance to platinum compounds is well documented. The resistance to platinum has been linked to the activity of divalent transporter ATP7B, which pumps platinum from the cytoplasm into lysosomes, decreasing its concentration in the cytoplasm. Several cancer models show increased expression of ATP7B; however, the reason for such an increase is not known. Here we show a strong positive correlation between mRNA levels of TMEM16A and ATP7B in human SCCHN tumors. TMEM16A overexpression and depletion in SCCHN cell lines caused parallel changes in the ATP7B mRNA levels. The ATP7B increase in TMEM16A-overexpressing cells was reversed by suppression of NADPH oxidase 2 (NOX2), by the antioxidant N-Acetyl-Cysteine (NAC) and by copper chelation using cuprizone and bathocuproine sulphonate (BCS). Pretreatment with either chelator significantly increased cisplatin's sensitivity, particularly in the context of TMEM16A overexpression. We propose that increased oxidative stress in TMEM16A-overexpressing cells liberates the chelated copper in the cytoplasm, leading to the transcriptional activation of ATP7B expression. This, in turn, decreases the efficacy of platinum compounds by promoting their vesicular sequestration. We think that such a new explanation of the mechanism of SCCHN tumors’ platinum resistance identifies novel approach to treating these tumors.

Collecting Words: A Clinical Example of a Morphology-Focused Orthographic Intervention

2020 ◽  
Vol 51 (3) ◽  
pp. 544-560 ◽  
Author(s):  
Kimberly A. Murphy ◽  
Emily A. Diehm
Keyword(s):  
Written Language ◽  
Morphological Knowledge ◽  
English Orthography ◽  
Word Level ◽  
Novel Approach ◽  
Language Pathology ◽  
The One ◽  
Critical Intervention ◽  
Reading And Spelling ◽  
Reading And Spelling Difficulties

Purpose Morphological interventions promote gains in morphological knowledge and in other oral and written language skills (e.g., phonological awareness, vocabulary, reading, and spelling), yet we have a limited understanding of critical intervention features. In this clinical focus article, we describe a relatively novel approach to teaching morphology that considers its role as the key organizing principle of English orthography. We also present a clinical example of such an intervention delivered during a summer camp at a university speech and hearing clinic. Method Graduate speech-language pathology students provided a 6-week morphology-focused orthographic intervention to children in first through fourth grade ( n = 10) who demonstrated word-level reading and spelling difficulties. The intervention focused children's attention on morphological families, teaching how morphology is interrelated with phonology and etymology in English orthography. Results Comparing pre- and posttest scores, children demonstrated improvement in reading and/or spelling abilities, with the largest gains observed in spelling affixes within polymorphemic words. Children and their caregivers reacted positively to the intervention. Therefore, data from the camp offer preliminary support for teaching morphology within the context of written words, and the intervention appears to be a feasible approach for simultaneously increasing morphological knowledge, reading, and spelling. Conclusion Children with word-level reading and spelling difficulties may benefit from a morphology-focused orthographic intervention, such as the one described here. Research on the approach is warranted, and clinicians are encouraged to explore its possible effectiveness in their practice. Supplemental Material https://doi.org/10.23641/asha.12290687

Sign in / Sign up

Export Citation Format

Share Document