A&P Seminar - Divita Mathur

The Analytical and Physical Seminar Series presents: Divita Mathur

Case Western Reserve University

Host: Devleena Samanta

Title: Programmable DNA nanoparticles for gene therapies

Location: WEL 2.122

Refreshments served at 3:15pm

Synthetic DNA nanotechnology enables the construction of precisely defined nanoscale architectures with broad applications in biotechnology and materials science. Here, we introduce gene-encoded DNA nanoparticles, in which the long single-stranded scaffold of DNA origami is engineered to encode protein-coding sequences, enabling structurally defined nanoparticles that function as gene templates. We demonstrate that these DNA nanoparticles support protein expression in both cell-free transcription–translation systems and mammalian cells. Using prototypical reporter proteins, we establish that complex three-dimensional DNA architectures remain accessible to transcriptional machinery. Notably, we encode and express functional base editors from DNA nanoparticles and demonstrate their ability to mediate gene editing in mammalian cells. This eliminates the gene payload limitations associated with viral nanoparticles, which can only deliver ~4.2 kb genes. We further investigate how sequence design, staple strand composition, and nanoparticle architecture influence expression efficiency, identifying key design parameters governing transcriptional output. These results position gene-encoded DNA nanoparticles as a programmable platform for gene delivery and genome engineering.