He was co-founder of General Sentiment, a social media and news analytics company, and served as chief science officer from 2009 until it shut down in 2015.

"[4] Skiena has worked on algorithmic problems in synthetic biology, and, in particular, issues of optimal gene design for a given protein under various constraints.

In collaboration with virologist Eckard Wimmer, he has worked to computationally design synthetic viruses for use as attenuated vaccines.

A popular account of this work appears in Dennis Shasha and Cathy Lazare's Natural Computing.

[8] Their design, a tablet featuring a touch screen, GPS, and wireless communications was similar in many regards to the iPad as released by Apple in 2010.