Synthetic Biology—Toward Therapeutic Solutions. Issue 5 (27th February 2016)

• Record Type: Journal Article
• Authors: Haellman, Viktor; Fussenegger, Martin
• Is Part Of: Journal of molecular biology. Volume 428:Issue 5 Part B(2016:Mar. 01)
• Page Start: 945
• Page End: 962
• Publication Date: 2016-02-27
• Subjects: HSC hematopoietic stem cell -- ZF zinc finger -- TALE transcription activator-like effector -- CRISPR clustered regular interspaced short palindromic repeat -- RNAi RNA interference -- GPCR G-protein-coupled receptor -- GLP-1 glucagon-like peptide 1 -- ANP atrial natriuretic peptide -- NFAT nuclear factor of activated T cells -- PPARα peroxisome proliferator-activated receptor α -- TCR T-cell receptor -- CAR chimeric antigen receptor; synthetic biology; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2015.08.020
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: Higher multicellular organisms have evolved sophisticated intracellular and intercellular biological networks that enable cell growth and survival to fulfill an organism's needs. Although such networks allow the assembly of complex tissues and even provide healing and protective capabilities, malfunctioning cells can have severe consequences for an organism's survival. In humans, such events can result in severe disorders and diseases, including metabolic and immunological disorders, as well as cancer. Dominating the therapeutic frontier for these potentially lethal disorders, cell and gene therapies aim to relieve or eliminate patient suffering by restoring the function of damaged, diseased, and aging cells and tissues via the introduction of healthy cells or alternative genes. However, despite recent success, these efforts have yet to achieve sufficient therapeutic effects, and further work is needed to ensure the safe and precise control of transgene expression and cellular processes. In this review, we describe the biological tools and devices that are at the forefront of synthetic biology and discuss their potential to advance the specificity, efficiency, and safety of the current generation of cell and gene therapies, including how they can be used to confer curative effects that far surpass those of conventional therapeutics. We also highlight the current therapeutic delivery tools and the current limitations that hamper their use in human applications. Graphical Abstract: Highlights: Overview of the most prominent synthetic transcriptional, translational, and post-translational control devices. Critical assessment of advances and limitations of synthetic control devices for future gene- and cell-based therapies. Engineering living cells as theranostic devices that autonomously diagnose and treat diseases. Advances in safe and efficient delivery of gene- and cell-based medicines.