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Xie, Liji; Xie, Zhixun

doi:10.4194/1303-2712-v18_6_01

Cited by 6 publications

(6 citation statements)

References 15 publications

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“…Although still nascent, magnetic particle-meditated, targeted drug delivery systems have been widely developed for many biomedical applications. 22,23 Superparamagnetic nanoparticles, especially, have been explored to label MSCs and delivery them to local sites by applying an external magnetic field. 24 Following the success of magnetic cell delivery, we introduced magnetic nanoparticles to transform the cells with magnetic targeting groups for myocardial repair.…”

Section: Stem Cell Transformationsmentioning

confidence: 99%

Chemical Engineering of Cell Therapy for Heart Diseases

Cheng

2019

Acc. Chem. Res.

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Cardiovascular disease (CVD) is a major health problem worldwide. Since adult cardiomyocytes irreversibly withdraw from the cell cycle soon after birth, it is hard for cardiac cells to proliferate and regenerate after myocardial injury, such as that caused myocardial infarction (MI). Live cellbased therapies, which we term as first generation of therapeutic strategies, have been widely used for the treatment of many diseases, including CVD. However, cellular approaches have the problems of poor retention of the transplanted cells and the significant entrapment of the cells in the lungs when delivered intravenously. Another big problem is the low storage/shipping stability of live cells, which limits the manufacturability of living cell products. The field of chemical engineering focuses on designing large-scale processes to convert chemicals, raw materials, living cells, microorganisms, and energy into useful forms and products. By definition, chemical engineers conceive and design processes to produce, transform, and transport materials. This matches the direction that cell therapies are heading toward: "produce", from live cells to synthetic artificial cells; "transform", from bare cells to cell/matrix/factor combinations; and "transport". from simple systemic injections to targeted delivery. Thus, we hereby introduce the "chemical engineering of cell therapies" as a concept.

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Section: Stem Cell Transformationsmentioning

confidence: 99%

Chemical Engineering of Cell Therapy for Heart Diseases

Cheng

2019

Acc. Chem. Res.

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“…The challenges associated with the synthesis of such modified proteins in vitro certainly include the selection of ribosomes which continue to recognize the canonical α-L-amino acids that will constitute the majority of amino acids present in the modified proteins, while also enabling the structurally novel amino acids to be incorporated. In addition, to be utilized in cellulo the modified amino acids will have to be attached to a suitable tRNA, presumably by engineered aminoacyl-tRNA synthetases [41][42][43][44][45][46][47][48][49][50] or ribozymes. [36][37][38][39][40] Cellular incorporation will presumably also require recognition by cellular factors such as elongation factor Tu.…”

Section: Opportunities and Challengesmentioning

confidence: 99%

“…While native aminoacyl-tRNA synthetases assure a good level of fidelity in the activation of individual tRNA isoacceptors with their cognate amino acids, there are now multiple methods for activating individual tRNAs with non-canonical amino acids. These include chemical methods [31][32][33][34][35][36][37][38][39][40] and the use of sets of orthogonal tRNAs and aminoacyl-tRNA synthetases [41][42][43][44][45][46][47][48][49][50] which recognize canonical amino acids poorly if at all, and thus can be employed to introduce noncanonical amino acids into proteins. This strategy effectively bypasses the main mechanism for excluding non-canonical amino acids from proteins synthesized ribosomally.…”

Section: Introductionmentioning

confidence: 99%

Expanding the Scope of Protein Synthesis Using Modified Ribosomes

Dedkova

Hecht

2019

J. Am. Chem. Soc.

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The ribosome produces all of the proteins and many of the peptides present in cells. As a macromolecular complex comprised of both RNAs and proteins, it employs a constituent RNA to catalyze the formation of peptide bonds rapidly and with high fidelity. Thus the ribosome can be argued to represent the key link between the RNA World, in which RNAs were the primary catalysts, and present biological systems in which protein catalysts predominate. In spite of the well known phylogenetic conservation of ribosomal RNAs through evolutionary history, ribosomal RNAs can be altered readily when placed under suitable pressure, e.g. in the presence of antibiotics which bind to functionally critical regions of rRNAs. While the structures of rRNAs have been altered intentionally for decades to enable the study of their role(s) in the mechanism of peptide bond formation, it is remarkable that the purposeful alteration of rRNA structure to enable the elaboration of proteins and peptides containing non-canonical amino acids has occurred only recently. In this Perspective, we summarize the history of rRNA modifications, and demonstrate how the intentional modification of 23S rRNA in regions critical for peptide bond formation now enables the direct ribosomal incorporation of D-amino acids, β-amino acids, dipeptides and dipeptidomimetic analogues of the normal proteinogenic L-α-amino acids. While proteins containing metabolically important functional groups such as carbohydrates and phosphate groups are normally elaborated by the post-translational modification of nascent polypeptides, the use of modified ribosomes to produce such polymers directly is also discussed. Finally, we describe the elaboration of such modified proteins both in vitro and in bacterial cells, and suggest how such novel biomaterials may be exploited in future studies.

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“…scaffolds) have lower structural diversity. 24 Extensive research efforts have been dedicated to alleviate this problem by developing new DNA-compatible chemistry, 25 constructing DECLs with variable scaffolds, [26][27][28] natural product derived DECLs, [29][30][31] and building libraries in which different reactions are performed during a synthesis cycle. 32,33 We aim to address the challenge of low-diversity substructures at the level of hit-to-lead development instead of during DECL construction.…”

mentioning

confidence: 99%

Integrating DNA-encoded chemical libraries with virtual combinatorial library screening: Optimizing a PARP10 inhibitor

Lemke

Ravenscroft

Rueb

et al. 2020

Bioorganic & Medicinal Chemistry Letters

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Two critical steps in drug development are 1) the discovery of molecules that have the desired effects on a target, and 2) the optimization of such molecules into lead compounds with the required potency and pharmacokinetic properties for translation. DNA-encoded chemical libraries (DECLs) can nowadays yield hits with unprecedented ease, and lead-optimization is becoming the limiting step. Here we integrate DECL screening with structure-based computational methods to streamline the development of lead compounds. The presented workflow consists of enumerating a virtual combinatorial library (VCL) derived from a DECL screening hit and using computational binding prediction to identify molecules with enhanced properties relative to the original DECL hit. As proof-of-concept demonstration, we applied this approach to identify an inhibitor of PARP10 that is more potent and druglike than the original DECL screening hit.

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Cited by 6 publications

References 15 publications

Chemical Engineering of Cell Therapy for Heart Diseases

Chemical Engineering of Cell Therapy for Heart Diseases

Expanding the Scope of Protein Synthesis Using Modified Ribosomes

Integrating DNA-encoded chemical libraries with virtual combinatorial library screening: Optimizing a PARP10 inhibitor

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