INTRODUCTION: mRNA therapeutics were a niche area in drug development before COVID vaccines. They are now used in vaccine development, for non-viral therapeutic genome editing, AREAS COVERED: This article covers how to design, select, and develop an LNP for therapeutic genome editing in the liver. The roadmap is divided into selecting the right LNP for discovery via a design, make, test, and analyze cycle (DMTA). The design elements are focused on ionizable lipids in a 4-component LNP, and insights are provided for how to set an EXPERT OPINION: The perspective discusses the impact that academic-industry collaborations can have on developing new medicines for therapeutic genome editing in the liver. From the cited collaborations an enhanced understanding of intracellular trafficking, notably endosomal escape, and the internal structure of LNPs were attained and are deemed key to designing effective and safe LNPs. The knowledge gained will also enable additional assays and structural activity relationships, which would lead to the design of the next-generation delivery systems for nucleic acid therapies.