Precise protein expression through microRNA-mediated gene dosage compensation

Subjects

Transgene expression in cells and organisms underpins much of modern biological research. However, most commonly used expression systems generate broad and poorly controlled distributions of protein levels, leading to inaccurate experimental results and, in some contexts, overexpression-associated toxicity. These limitations complicate both quantitative biology and therapeutic applications, for which precise control of protein dosage is essential.

DIMMERs provide tuneable control of protein expression through modular design parameters, including the degree of miRNA–target complementarity, and miRNA copy number. An empirically derived miRNA design algorithm further extends the method from single-gene regulation to simultaneous regulation of multiple genes, thereby enabling the construction of defined protein expression ‘cocktails’ within the same cell. Importantly, DIMMERs are compatible with diverse cell types and delivery methods.

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