Safeguarding Synthetic Biology

Since the emergence of SARS-CoV-2, humanity has witnessed the strengths and weaknesses of current antiviral strategies. Vaccines have saved millions of lives, yet their production, distribution, and time-dependent immunity leave critical gaps. Synthetic biology holds the promise to solve some of the world’s most urgent problems, just like the ones we've faced in the past few years. Yet, as this power expands, so too does our responsibility to ensure that these technologies are used safely, securely, and equitably. In the context of global infectious disease, this responsibility becomes especially crucial. Our project explores how biological engineering can strengthen both biosafety and biosecurity, by focusing not on the virus, but on the host itself.

Multiple Layers of Control to Mitigate Risks

Synthetic biology’s greatest risks often arise from loss of control, and to mitigate this, our CRISPRa system integrates multiple layers of control.

  1. First, the activation mechanism controlled solely by Dox reduces the risk of off-target and leaky expression of the system, and by choosing our gene targets specifically, we can reduce the overall cytotoxic and inflammatory effects that would usually develop as a natural consequence of immune activation.
  2. Secondly, by using only biodegradable materials like Poloxamer-407, and non-integrating plasmids, we ensure that our system degrades over time, preventing persistence and any long-term consequences of our gene modulation.
  3. Third, and perhaps most importantly though, by targeting host pathways, we avoid selective pressure that can lead to viral escape mutants. Already, we are facing crises as pathogens outcompete us with their quick evolution, be it the antibiotic race against bacteria or the rush to find drugs that can effectively bind to viral proteins. However, upregulating the existing host defenses that viruses find necessary to hijack, we reduce the possibility that they can find ways to circumvent our solutions.

Our Vision: A Blueprint for Safe Genetic Interventions

Our vision extends beyond this antiviral project. Host-directed CRISPRa can serve as a blueprint for safe, modular genetic interventions. By establishing frameworks where activation is conditional, localized, and reversible, synthetic biology can move toward therapeutic precision without genetic permanence. This approach empowers local communities to adapt CRISPRa safely for region-specific pathogens while maintaining biosafety standards.

Synthetic biology’s potential to transform health is undeniable, but its sustainability depends on our commitment to safety, security, and ethics. Our Host-Directed CRISPRa project demonstrates that safety and innovation can coexist. By emphasizing control, transience, and biosafe design, we create not just an antiviral tool, but a model for responsible biological engineering.