Synthetic biology and therapeutic strategies for the degenerating brain: Synthetic biology approaches can transform classical cell and gene therapies, to provide new cures for neurodegenerative diseases

Abstract

Synthetic biology is an emerging engineering discipline that attempts to design and rewire biological components, so as to achieve new functions in a robust and predictable manner. The new tools and strategies provided by synthetic biology have the potential to improve therapeutics for neurodegenerative diseases. In particular, synthetic biology will help design small molecules, proteins, gene networks, and vectors to target disease-related genes. Ultimately, new intelligent delivery systems will provide targeted and sustained therapeutic benefits. New treatments will arise from combining 'protect and repair' strategies: the use of drug treatments, the promotion of neurotrophic factor synthesis, and gene targeting. Going beyond RNAi and artificial transcription factors, site-specific genome modification is likely to play an increasing role, especially with newly available gene editing tools such as CRISPR/Cas9 systems. Taken together, these advances will help develop safe and long-term therapies for many brain diseases in human patients.

Keywords: artificial cell systems; genome editing; neurodegeneration; synthetic proteins.

Figure 1

Overcoming the blood brain barrier for therapy. The sketch shows the cellular components of the blood brain barrier (BBB), which isolates and protects the neural tissue. The barrier prevents most drugs and therapeutic molecules from reaching their target sites in the central nervous system, when administered peripherally. Several strategies can be used to overcome the BBB, although these vary in their invasiveness. Recent developments include the use of nanoparticles and ‘Trojan peptides’ that naturally pass through lipid membranes to deliver their cargo. For a recent review of advances in delivery systems to the central nervous system, see .

Figure 2

Overview of synthetic biology approaches for tackling neurodegenerative diseases. The sketch shows a marble bust of Hippocrates, who recorded some of the earliest insights about the functions of the brain. Note that many of the approaches can be used in combination.