scholarly journals Images in cardiovascular medicine. Detection of exogenous gene expression in live adult ventricular myocytes after adenoviral gene delivery.

Circulation ◽  
1994 ◽  
Vol 90 (4) ◽  
pp. 2124-2125 ◽  
Author(s):  
L A Kirshenbaum ◽  
K J Angelides ◽  
M D Schneider
Keyword(s):  
Gene Expression ◽  
Gene Delivery ◽  
Ventricular Myocytes ◽  
Cardiovascular Medicine ◽  
Adenoviral Gene Delivery ◽  
Exogenous Gene

scholarly journals The proper strategy to compress and protect plasmid DNA in the Pluronic L64-electropulse system for enhanced intramuscular gene delivery

2019 ◽  
Vol 6 (5) ◽  
pp. 289-298 ◽  
Author(s):  
Yutong He ◽  
Yili Liu ◽  
Zhe Sun ◽  
Fei Han ◽  
James Zhenggui Tang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Delivery ◽  
Natural Compound ◽  
Epigallocatechin Gallate ◽  
Proof Of Concept ◽  
Delivery Method ◽  
Promising Strategy ◽  
Cationic Materials ◽  
Exogenous Gene

Abstract Intramuscular expression of functional proteins is a promising strategy for therapeutic purposes. Previously, we developed an intramuscular gene delivery method by combining Pluronic L64 and optimized electropulse, which is among the most efficient methods to date. However, plasmid DNAs (pDNAs) in this method were not compressed, making them unstable and inefficient in vivo. We considered that a proper compression of pDNAs by an appropriate material should facilitate gene expression in this L64-electropulse system. Here, we reported our finding of such a material, Epigallocatechin gallate (EGCG), a natural compound in green teas, which could compress and protect pDNAs and significantly increase intramuscular gene expression in the L64-electropulse system. Meanwhile, we found that polyethylenimine (PEI) could also slightly improve exogenous gene expression in the optimal procedure. By analysing the characteristic differences between EGCG and PEI, we concluded that negatively charged materials with strong affinity to nucleic acids and/or other properties suitable for gene delivery, such as EGCG, are better alternatives than cationic materials (like PEI) for muscle-based gene delivery. The results revealed that a critical principle for material/pDNA complex benefitting intramuscular gene delivery/expression is to keep the complex negatively charged. This proof-of-concept study displays the breakthrough in compressing pDNAs and provides a principle and strategy to develop more efficient intramuscular gene delivery systems for therapeutic applications.

Adenoviral gene delivery of interleukin-10 inhibits kupffer cells avtivation in vitro

2007 ◽  
Vol 45 (01) ◽  
Author(s):  
P Walbrun ◽  
S Netter ◽  
R Wiest ◽  
E Gäbele ◽  
J Schölmerich ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Kupffer Cells ◽  
Interleukin 10 ◽  
Adenoviral Gene Delivery

CARP Plays a Key Role in Cellular Growth Under Hypertrophic Stimuli in Neonatal Rat Ventricular Myocytes

2013 ◽  
Vol 9 ◽  
Author(s):  
Tara A Shrout
Keyword(s):  
Gene Expression ◽  
Ventricular Myocytes ◽  
Cellular Growth ◽  
Neonatal Rat ◽  
Transcriptional Level ◽  
Dual Nature ◽  
Hypertrophic Growth ◽  
Rat Ventricular Myocytes ◽  
Neonatal Rat Ventricular Myocytes ◽  
Over Time

Cardiac hypertrophy is a growth process that occurs in response to stress stimuli or injury, and leads to the induction of several pathways to alter gene expression. Under hypertrophic stimuli, sarcomeric structure is disrupted, both as a consequence of gene expression and local changes in sarcomeric proteins. Cardiac-restricted ankyrin repeat protein (CARP) is one such protein that function both in cardiac sarcomeres and at the transcriptional level. We postulate that due to this dual nature, CARP plays a key role in maintaining the cardiac sarcomere. GATA4 is another protein detected in cardiomyocytes as important in hypertrophy, as it is activated by hypertrophic stimuli, and directly binds to DNA to alter gene expression. Results of GATA4 activation over time were inconclusive; however, the role of CARP in mediating hypertrophic growth in cardiomyocytes was clearly demonstrated. In this study, Neonatal Rat Ventricular Myocytes were used as a model to detect changes over time in CARP and GATA4 under hypertrophic stimulation by phenylephrine and high serum media. Results were detected by analysis of immunoblotting. The specific role that CARP plays in mediating cellular growth under hypertrophic stimuli was studied through immunofluorescence, which demonstrated that cardiomyocyte growth with hypertrophic stimulation was significantly blunted when NRVMs were co-treated with CARP siRNA. These data suggest that CARP plays an important role in the hypertrophic response in cardiomyocytes.

scholarly journals Chronic Elevation of Calmodulin in the Ventricles of Transgenic Mice Increases the Autonomous Activity of Calmodulin-Dependent Protein Kinase II, Which Regulates Atrial Natriuretic Factor Gene Expression

2000 ◽  
Vol 14 (8) ◽  
pp. 1125-1136 ◽  
Author(s):  
Josep M. Colomer ◽  
Anthony R. Means
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Transgenic Mice ◽  
Atrial Natriuretic Factor ◽  
Ventricular Myocytes ◽  
Dependent Protein Kinase ◽  
Natriuretic Factor ◽  
Dependent Protein ◽  
Autonomous Activity

Abstract Although isoforms of Ca2+/calmodulin-dependent protein kinase II (CaMKII) have been implicated in the regulation of gene expression in cultured cells, this issue has yet to be addressed in vivo. We report that the overexpression of calmodulin in ventricular myocytes of transgenic mice results in an increase in the Ca2+/calmodulin-independent activity of endogenous CaMKII. The calmodulin transgene is regulated by a 500-bp fragment of the atrial natriuretic factor (ANF) gene promoter which, based on cell transfection studies, is itself known to be regulated by CaMKII. The increased autonomous activity of CaMKII maintains the activity of the transgene and establishes a positive feedforward loop, which also extends the temporal expression of the endogenous ANF promoter in ventricular myocytes. Both the increased activity of CaMKII and transcriptional activation of ANF are highly selective responses to the chronic overexpression of calmodulin. These results indicate that CaMKII can regulate gene expression in vivo and suggest that this enzyme may represent the Ca2+-dependent target responsible for reactivation of the ANF gene during ventricular hypertrophy.

scholarly journals Physical positioning markedly enhances brain transduction after intrathecal AAV9 infusion

2018 ◽  
Vol 4 (11) ◽  
pp. eaau9859 ◽  
Author(s):  
Michael J. Castle ◽  
Yuhsiang Cheng ◽  
Aravind Asokan ◽  
Mark H. Tuszynski
Keyword(s):  
Gene Expression ◽  
Gene Delivery ◽  
Neurological Disorders ◽  
Fold Increase ◽  
Brain Regions ◽  
Intrathecal Administration ◽  
Simple Method ◽  
Virus Serotype ◽  
Cortical Regions ◽  
The Brain

Several neurological disorders may benefit from gene therapy. However, even when using the lead vector candidate for intrathecal administration, adeno-associated virus serotype 9 (AAV9), the strength and distribution of gene transfer to the brain are inconsistent. On the basis of preliminary observations that standard intrathecal AAV9 infusions predominantly drive reporter gene expression in brain regions where gravity might cause cerebrospinal fluid to settle, we tested the hypothesis that counteracting vector “settling” through animal positioning would enhance vector delivery to the brain. When rats are either inverted in the Trendelenburg position or continuously rotated after intrathecal AAV9 infusion, we find (i) a significant 15-fold increase in the number of transduced neurons, (ii) a marked increase in gene delivery to cortical regions, and (iii) superior animal-to-animal consistency of gene expression. Entorhinal, prefrontal, frontal, parietal, hippocampal, limbic, and basal forebrain neurons are extensively transduced: 95% of transduced cells are neurons, and greater than 70% are excitatory. These findings provide a novel and simple method for broad gene delivery to the cortex and are of substantial relevance to translational programs for neurological disorders, including Alzheimer’s disease and related dementias, stroke, and traumatic brain injury.

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