An emerging type of material called a metal-organic framework (MOF) could help improve the delivery of genetic material for treating disease.

MOFs are hybrid materials constructed from metal ions linked by organic molecules. In biomedicine, they have mostly been used as delivery vehicles for small-molecule pharmaceuticals, but now a KAUST-led team has developed a MOF-based system for getting DNA across cell membranes into target cells.

The researchers built their MOFs using a collection of nucleic acid and unnatural amino acid building blocks tethered together by zinc atoms, assembled in a pyramid-like array. They loaded up the resulting materials with single-stranded DNA. The structures protected the genetic cargo from enzymatic degradation and helped ferry the single-stranded DNA into cells, where it ended up inside the nucleus — the cell’s inner sanctum where all gene activity takes place.

A critical challenge in gene therapy remains the safe and effective delivery of genetic materials, and most methods in use today are costly, inefficient, imprecise or potentially toxic. The KAUST-devised delivery system could offer an improved means of regulating gene expression and function in people’s cells as a way of treating cancer, hemophilia and many more genetic disorders.