Synthetic Biology Approaches for Engineering Next-Generation Adenoviral Gene Therapies

ACS Nano ◽  
2021 ◽  
Author(s):  
Logan Thrasher Collins ◽  
David T. Curiel
2016 ◽  
Vol 9 (2) ◽  
pp. 328-330
Author(s):  
Steven Sorscher

Next-generation sequencing (NGS) of tumors has been heralded as a promising tool to identify ‘actionable’ abnormalities susceptible to therapies targeting these mutated genes. Inhibiting the oncoprotein expressed from a single dominant mutated gene (oncogene) forms the basis for the success of most of the targeted gene therapies approved in the last several years. The well over 20 FDA-approved kinase inhibitors for cancer treatment are examples [Janne et al.: Nat Rev Drug Discov 2009;8: 709–723]. These and other similar agents in development might prove effective therapies for tumors originating from tissues other than those for which these drugs are currently approved. Finding such mutations in tumors of patients through NGS is being aggressively pursued by patients and their oncologists. For identified mutated tumor suppressor genes (TSG) the challenge is really the opposite. Rather than inhibiting the action of an oncoprotein, targeting would involve restoring the activity of the wild-type (WT) TSG function [Knudson: Proc Natl Acad Sci USA 1971;249: 912–915]. Here, a case is reported that illustrates the implications of a mutated TSG (BRIP1) identified by NGS as potentially actionable. In such cases, measuring allelic mutation frequency potentially allows for the identification of tumors where the loss of heterozygosity of a TSG exists. Without substantial loss of expression of the WT TSG product, it would seem very unlikely that ‘replacing’ a WT TSG product that is not a lost product would be a useful therapy.


2010 ◽  
Vol 2010 ◽  
pp. 1-18 ◽  
Author(s):  
Laura R. Jarboe ◽  
Xueli Zhang ◽  
Xuan Wang ◽  
Jonathan C. Moore ◽  
K. T. Shanmugam ◽  
...  

Production of fuels and chemicals through microbial fermentation of plant material is a desirable alternative to petrochemical-based production. Fermentative production of biorenewable fuels and chemicals requires the engineering of biocatalysts that can quickly and efficiently convert sugars to target products at a cost that is competitive with existing petrochemical-based processes. It is also important that biocatalysts be robust to extreme fermentation conditions, biomass-derived inhibitors, and their target products. Traditional metabolic engineering has made great advances in this area, but synthetic biology has contributed and will continue to contribute to this field, particularly with next-generation biofuels. This work reviews the use of metabolic engineering and synthetic biology in biocatalyst engineering for biorenewable fuels and chemicals production, such as ethanol, butanol, acetate, lactate, succinate, alanine, and xylitol. We also examine the existing challenges in this area and discuss strategies for improving biocatalyst tolerance to chemical inhibitors.


2021 ◽  
Author(s):  
Mibel Aguilar ◽  
Patricia Bassereau ◽  
Margarida Bastos ◽  
Paul Beales ◽  
Burkhard Bechinger ◽  
...  

Processes ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 214 ◽  
Author(s):  
Julio R. Banga ◽  
Filippo Menolascina

Synthetic biology—the engineering of cells to rewire the biomolecular networks inside them—has witnessed phenomenal progress [...]


2015 ◽  
Vol 58 (7) ◽  
pp. 658-665 ◽  
Author(s):  
Ran Chao ◽  
YongBo Yuan ◽  
HuiMin Zhao

2021 ◽  
Author(s):  
Roger Rubio-Sánchez ◽  
Simone Eizagirre Barker ◽  
Michal Walczak ◽  
Pietro Cicuta ◽  
Lorenzo Di Michele

AbstractCell membranes regulate the distribution of biological machinery between phase-separated lipid domains to facilitate key processes including signalling and transport, which are among the life-like functionalities that bottom-up synthetic biology aims to replicate in artificial-cellular systems. Here, we introduce a modular approach to program partitioning of amphiphilic DNA nanostructures in co-existing lipid domains. Exploiting the tendency of different hydrophobic “anchors” to enrich different phases, we modulate the lateral distribution of our devices by rationally combining hydrophobes, and by changing nanostructure size and its topology. We demonstrate the functionality of our strategy with a bio-inspired DNA architecture, which dynamically undergoes ligand-induced reconfiguration to mediate cargo transport between domains via lateral re-distribution. Our findings pave the way to next-generation biomimetic platforms for sensing, transduction, and communication in synthetic cellular systems.


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