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. Author manuscript; available in PMC: 2024 May 10.
Published in final edited form as: ACS Appl Mater Interfaces. 2023 Apr 28;15(18):21877–21892. doi: 10.1021/acsami.3c01501

Figure 1.

Figure 1.

A LNP platform for small protein DARPin delivery was engineered using library screening to identify (i) ionizable lipids for potent DARPin delivery, and (ii) excipient and cargo molar ratios tailored for DARPin delivery. Using this LNP, a K27 DARPin—modified with a 30-repeat of negatively charged aspartic acid (D30)—can be delivered intracellularly, undergoing endosomal escape to become available in the cytosol. In screening applications, K27 modified with S11 complexes with GFP (1–10) in the reporter cell line to produce fluorescence. In functional applications, K27 binds to and inhibits RAS.