SARS-CoV-2 and other coronaviruses pose major threats to global health, yet computational efforts to understand them have largely overlooked the process of budding, a key part of the coronavirus life cycle. When expressed together, coronavirus M and E proteins are sufficient to facilitate budding into the ER-Golgi intermediate compartment (ERGIC). To help elucidate budding, we ran atomistic molecular dynamics (MD) simulations using the Feig laboratory’s refined structural models of the SARS-CoV-2 M protein dimer and E protein pentamer. Our MD simulations consisted of M protein dimers and E protein pentamers in patches of membrane. By examining where these proteins induced membrane curvature in silico , we obtained insights around how the budding process may occur. Multiple M protein dimers acted together to induce global membrane curvature through protein–lipid interactions while E protein pentamers kept the membrane planar. These results could eventually help guide development of antiviral therapeutics that inhibit coronavirus budding.

Gene therapy has demonstrated enormous potential for changing how we combat disease. By directly engineering the genetic composition of cells, it provides a broad range of options for improving human health. Adeno-associated viruses (AAVs) represent a leading gene therapy vector and are expected to address a wide range of conditions in the coming decade. Three AAV therapies have already been approved by the FDA to treat Leber’s congenital amaurosis, spinal muscular atrophy, and hemophilia B. Yet these therapies cost around $850,000, $2,100,000, and $3,500,000, respectively. Such prices limit the broad applicability of AAV gene therapy and make it inaccessible to most patients. Much of this problem arises from the high manufacturing costs of AAVs. At the same time, the field of synthetic biology has grown rapidly and has displayed a special aptitude for addressing biomanufacturing problems. Here, we discuss emerging efforts to apply synthetic biology design to decrease the price of AAV production, and we propose that such efforts could play a major role in making gene therapy much more widely accessible.

Synthetic biology centers on the design and modular assembly of biological parts so as to construct artificial biological systems. Over the past decade, synthetic biology has blossomed into a highly productive field, yielding advances in diverse areas such as neuroscience, cell-based therapies, and chemical manufacturing. Similarly, the field of gene therapy has made enormous strides both in proof-of-concept studies and in the clinical setting. One viral vector of increasing interest for gene therapy is the adenovirus (Ad). A major part of the Ad's increasing momentum comes from synthetic biology approaches to Ad engineering. Convergence of gene therapy and synthetic biology has enhanced Ad vectors by mitigating Ad toxicity in vivo, providing precise Ad tropisms, and incorporating genetic circuits to make smart therapies which adapt to environmental stimuli. Synthetic biology engineering of Ad vectors may lead to superior gene delivery and editing platforms which could find applications in a wide range of therapeutic contexts.

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