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.

Highlights

  • ‘Our pleasures, joys, laughter, and jests arise from no other source than the brain; and so do our pains, grief, anxieties, and tears.’ Two millennia after Hippocrates first acknowledged this simple truth, understanding how the brain works is still one of our major challenges

  • In a rat model of Parkinson’s disease (PD), a synthetic zinc finger (ZF) coupled to the activator domain targeting the endogenous glial-derived neurotrophic factor (GDNF) promoter, was neuroprotective [58]

  • Synthetic biology can provide many useful approaches for the rational design of therapeutic factors and intelligent systems to treat a variety of diseases, including targeting the most complicated organ in our body, the brain

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Summary

Introduction

‘Our pleasures, joys, laughter, and jests arise from no other source than the brain; and so do our pains, grief, anxieties, and tears.’ Two millennia after Hippocrates first acknowledged this simple truth, understanding how the brain works is still one of our major challenges. Putting aside our limited understanding of neural circuit functions, the intricate mixture of cell types populating the brain, the difficulty of targeted delivery, and the problem of designing drugs capable of crossing the blood brain barrier effectively (Fig. 1), we still face the daunting problem of rewiring and restoring the neural circuits when some of their components are lost as a result of degeneration. To circumvent this problem, it is critical to make the earliest possible interventions, ideally before neurodegeneration takes place.

Trojan peptides
How will gene therapy conquer neurodegenerative diseases?
IF b
Improvement with synthetic biology tools
Fully synthetic antisense oligonucleotides
Eukaryotic transcription factor motifs
Easy to engineer Full modularity to make long chains
Engineering approaches improve the clearance of aberrant proteins
Genome editing for neurodegenerative disease models
Findings
Conclusions and outlook
Full Text
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