Fig. 2: Gene therapy foam boosts transfection rates and permits precise payload delivery to defined locations.

a–d Screening of various foam vehicles to enhance topical gene delivery. Lipid nanoparticles (LNPs) carrying firefly luciferase-encoding mRNA were mixed with foam precursor solutions composed of 0.8 wt % methylcellulose, sodium caseinate (Na caseinate), or albumin. Prepared foam was added on top of cultured HeLa cells, or cells were transfected with an equal dose of LNPs suspended in PBS. a In vitro bioluminescent imaging of cells exposed to LNP suspension or LNP foam. Boxplots summarizing luciferase signals from horizontal (b) and angled (c) transfections. On each box plot, the central mark indicates the median, and the bottom and top edges of the box indicate the interquartile range. Whiskers represent 95% confidence intervals. b *P < 0.0001; **P < 0.0001; ***P = 0.0004. c *P < 0.0001; **P = 0.0014; ***P < 0.0001. Images of cell culture dishes shown on the left of a were created with BioRender.com. (d) Quantification of viable (trypan blue-excluding) HeLa cells following horizonal or angled transfections with PBS or methylcellulose foam. On each box plot, the central mark indicates the median, and the bottom and top edges of the box indicate the interquartile range. Whiskers represent 95% confidence intervals. Pairwise differences between the groups were statistically analyzed using the unpaired, two-tailed Student’s t test. P < 0.05 was considered significant. Ns., non-significant. N = 6 biologically independent samples. e Photos and corresponding bioluminescence images of cell culture dishes seeded with HeLa cells. The text “FRED HUTCH” was written onto cells using syringes loaded either with LNP suspension or LNP foam, while holding the culture plates vertically. Bioluminescent signals were visualized 24 h later. The shown pictures represent four dishes each with similar outcomes. Source data are provided as a Source Data file.