Work

Efficient active transport of gene nanocarriers to the cell nucleus

Year: 2003

Type: article

Abstract: The intracellular transport of therapeutic gene carriers is poorly understood, limiting the rational design of efficient new vectors. We used live-cell real-time multiple particle tracking to quantify the intracellular transport of hundreds of individual nonviral DNA nanocarriers with 5-nm and 33-ms resolution. Unexpected parallels between several of nature's most efficient DNA viruses and nonviral polyethylenimine/DNA nanocomplexes were revealed to include motor protein-driven transport through the cytoplasm toward the nucleus on microtubules. Active gene carrier transport led to efficient perinuclear accumulation within minutes. The results provide direct evidence to dispute the common belief that the efficiency of nonviral gene carriers is dramatically reduced because of the need for their relatively slow random diffusion through the cell cytoplasm to the nucleus and, instead, focuses the attention of rational carrier design on overcoming barriers downstream of perinuclear accumulation.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.0636277100

Authors: Junghae Suh, Denis Wirtz, Justin Hanes

Institution: Johns Hopkins University

Language: English

Topic: RNA Interference and Gene Delivery

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Science Foundation, National Institutes of Health, National Institute of General Medical Sciences

Awards: G1032954840, Biomedical Engineering Training Program, NSE/NIRT: Nanoscale Sensing of Single Cell Surface Receptor Affinity for Individual Ligands