DNA Origami Inside-Out Viruses.

Area of Science:

• Synthetic biology
• Nanotechnology
• Structural DNA nanotechnology

Background:

• Viruses are natural nanoscale delivery systems, typically protein shells encapsulating nucleic acids with [3,5]-fold rotational symmetry.
• Existing synthetic virus platforms often mimic natural viral structures, limiting design flexibility.

Discussion:

• This study reports a synthetic topology for everted viruses, utilizing a single-stranded DNA hollow cube.
• The DNA cube exterior is functionalized with human immunodeficiency virus Trans-Activator of Transcription (HIV-Tat) transduction domains.
• A pH-responsive lid enables controlled encapsulation and release of functional proteins into target cells.

Key Insights:

• The synthetic cubes are [3,4]-fold DNA boxes, distinct from natural protein-based viruses.
• These DNA-built viruses are monodisperse nanoscale assemblies capable of infecting human cells.
• The platform allows for the targeted delivery of specialized protein cargo.

Outlook:

• This work presents a versatile bottom-up platform for engineering nonpolyhedral, nonprotein synthetic viruses.
• Potential applications include targeted drug delivery, gene therapy, and fundamental biological research.
• Further development could lead to novel biomimetic machines with tailored functionalities.