The most common gene regulation mechanism is when a protein binds to a regulatory sequence to change RNA transcription. However, these sequences are short relative to the genome length, so finding them poses a challenging search problem. This chapter presents two mathematical frameworks capturing different aspects of this problem. First, we study the interplay between diffusional flux through a target where the searching proteins get sequestered on DNA far from the target because of non-specific interactions. From this model, we derive a simple formula for the optimal protein-DNA unbinding rate, maximizing the particle flux. Second, we study how the flux flows through a target on a single antenna with variable length. Here, we identify a non-trivial logarithmic correction to the linear behavior relative to the target size proposed by Smoluchowski’s flux formula.