Cell Engineering of the Rat and Human Cysteine Conjugate Beta Lyase Genes and Applications to Nephrotoxicity Assessment

1999 ◽  
pp. 283-291
Author(s):  
G. Gordon Gibson ◽  
Peter S. Goldfarb ◽  
Laurie J. King ◽  
Ian Kitchen ◽  
Nick Plant ◽  
...  
Keyword(s):  
Cell Engineering

Programmable in vitro Co-Encapsidation of Guest Proteins Inside Protein Nanocages

2018 ◽  
Author(s):  
Noor H. Dashti ◽  
Rufika S. Abidin ◽  
Frank Sainsbury
Keyword(s):  
Self Assembly ◽  
Mammalian Cells ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Super Resolution ◽  
Cell Engineering ◽  
Particle Analysis ◽  
Protein Cages

Bioinspired self-sorting and self-assembling systems using engineered versions of natural protein cages have been developed for biocatalysis and therapeutic delivery. The packaging and intracellular delivery of guest proteins is of particular interest for both <i>in vitro</i> and <i>in vivo</i> cell engineering. However, there is a lack of platforms in bionanotechnology that combine programmable guest protein encapsidation with efficient intracellular uptake. We report a minimal peptide anchor for <i>in vivo</i> self-sorting of cargo-linked capsomeres of the Murine polyomavirus (MPyV) major coat protein that enables controlled encapsidation of guest proteins by <i>in vitro</i> self-assembly. Using Förster resonance energy transfer (FRET) we demonstrate the flexibility in this system to support co-encapsidation of multiple proteins. Complementing these ensemble measurements with single particle analysis by super-resolution microscopy shows that the stochastic nature of co-encapsidation is an overriding principle. This has implications for the design and deployment of both native and engineered self-sorting encapsulation systems and for the assembly of infectious virions. Taking advantage of the encoded affinity for sialic acids ubiquitously displayed on the surface of mammalian cells, we demonstrate the ability of self-assembled MPyV virus-like particles to mediate efficient delivery of guest proteins to the cytosol of primary human cells. This platform for programmable co-encapsidation and efficient cytosolic delivery of complementary biomolecules therefore has enormous potential in cell engineering.

Usefulness of collaboration between mathematical models and cell engineering for elucidating complex disease mechanisms and discover effective drugs

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Kohjitani ◽  
A Kashiwa ◽  
T Makiyama ◽  
F Toyoda ◽  
Y Yamamoto ◽  
...  
Keyword(s):  
Mathematical Model ◽  
In Silico ◽  
Complex Disease ◽  
Ion Selectivity ◽  
Public Institution ◽  
Cell Engineering ◽  
Funding Source ◽  
Patch Clamp Technique ◽  
In Silico Model

Abstract Background A missense mutation, CACNA1C-E1115K, located in the cardiac L-type calcium channel (LTCC), was recently reported to be associated with diverse arrhythmias. Several studies reported in-vivo and in-vitro modeling of this mutation, but actual mechanism and target drug of this disease has not been clarified due to its complex ion-mechanisms. Objective To reveal the mechanism of this diverse arrhythmogenic phenotype using combination of in-vitro and in-silico model. Methods and results Cell-Engineering Phase: We generated human induced pluripotent stem cell (hiPSC) from a patient carrying heterozygous CACNA1C-E1115K and differentiated into cardiomyocytes. Spontaneous APs were recorded from spontaneously beating single cardiomyocytes by using the perforated patch-clamp technique. Mathematical-Modeling Phase: We newly developed ICaL-mutation mathematical model, fitted into experimental data, including its impaired ion selectivity. Furthermore, we installed this mathematical model into hiPSC-CM simulation model. Collaboration Phase: Mutant in-silico model showed APD prolongation and frequent early afterdepolarization (EAD), which are same as in-vitro model. In-silico model revealed this EAD was mostly related to robust late-mode of sodium current occurred by Na+ overload and suggested that mexiletine is capable of reducing arrhythmia. Afterward, we applicated mexiletine onto hiPSC-CMs mutant model and found mexiletine suppress EADs. Conclusions Precise in-silico disease model can elucidate complicated ion currents and contribute predicting result of drug-testing. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists

Synthetic chemical ligands and cognate antibodies for biorthogonal drug targeting and cell engineering

2021 ◽  
Vol 170 ◽  
pp. 281-293
Author(s):  
Pere Monge ◽  
Ane Bretschneider Søgaard ◽  
Dante Guldbrandsen Andersen ◽  
Rona Chandrawati ◽  
Alexander N. Zelikin
Keyword(s):  
Drug Targeting ◽  
Cell Engineering

scholarly journals Development of a rabies virus-based retrograde tracer with high trans-monosynaptic efficiency by reshuffling glycoprotein

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Fan Jia ◽  
Li Li ◽  
Haizhou Liu ◽  
Pei Lv ◽  
Xiangwei Shi ◽  
...  
Keyword(s):  
Experimental Data ◽  
Rabies Virus ◽  
Oncolytic Virus ◽  
Neural Circuits ◽  
Bioinformatic Analysis ◽  
Cell Engineering ◽  
Bias Score ◽  
Codon Pair Bias ◽  
Codon Pair

AbstractRabies virus (RV) is the most widely used vector for mapping neural circuits. Previous studies have shown that the RV glycoprotein can be a target to improve the retrograde transsynaptic tracing efficiency. However, the current versions still label only a small portion of all presynaptic neurons. Here, we reshuffled the oG sequence, a chimeric glycoprotein, with positive codon pair bias score (CPBS) based on bioinformatic analysis of mouse codon pair bias, generating ooG, a further optimized glycoprotein. Our experimental data reveal that the ooG has a higher expression level than the oG in vivo, which significantly increases the tracing efficiency by up to 12.6 and 62.1-fold compared to oG and B19G, respectively. The new tool can be used for labeling neural circuits Therefore, the approach reported here provides a convenient, efficient and universal strategy to improve protein expression for various application scenarios such as trans-synaptic tracing efficiency, cell engineering, and vaccine and oncolytic virus designs.

T cell engineering for adoptive T cell therapy: safety and receptor avidity

2019 ◽  
Vol 68 (10) ◽  
pp. 1701-1712 ◽  
Author(s):  
Elvira D’Ippolito ◽  
Kilian Schober ◽  
Magdalena Nauerth ◽  
Dirk H. Busch
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Cell Engineering ◽  
Adoptive T Cell Therapy ◽  
T Cell Therapy ◽  
T Cell Engineering

scholarly journals Cell engineering by the internalization of bioinstructive micelles for enhanced bone regeneration

Nanomedicine ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. 1707-1721 ◽  
Author(s):  
Vítor E Santo ◽  
Juthamas Ratanavaraporn ◽  
Keisuke Sato ◽  
Manuela E Gomes ◽  
João F Mano ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Cell Engineering
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