The design of light-responsive bio-agents offers the means to control biology with exquisite temporal and spatial resolution. Conventional methods for controlling protein action, such as expression of mutants or silencing of gene expression, are poorly suited to probe the behavior of proteins in dynamic events, such as cell motility or division. Although optogenetics was originally developed to control the behavior of neuronal cells via light-responsive proteins, the definition has now broadened to include the application of any light-responsive protein to study and control dynamic cell biological behavior. Unfortunately, only a relatively few genetically engineered proteins whose behaviors are controlled by light have been described (primarily ion channels). Indeed, in spite of the promise that optogenetic tools hold for biology and medicine, their ready application is constrained by “protein engineering strategies that unfortunately remain in [the] development stage”. A straightforward optogenetic engineering approach for the design of genetically-encoded light-responsive proteins will be described.
The use of light to activate therapeutic agents at disease sites offers the advantage of aggressive treatment with exquisite spatial control, thereby reducing potential deleterious side effects at unintended sites. A major challenge in this regard is the so-called “optical window of tissue”, the wavelength of light that enjoys maximal tissue penetration, which lies in the range of 600 – 900 nm. We’ve developed a light-mediated drug delivery strategy that not only operates within the optical window of tissue, but also allows different drugs to be pre-assigned different wavelengths of activation, enabling differential communication with individual members of a family of phototherapeutics.