Silver, PamelaKready, Kasia2024-11-2020242024-09-052024Kready, Kasia. 2024. Engineering breastfeeding-compatible biologics to enhance lactation. Doctoral dissertation, Harvard University Graduate School of Arts and Sciences.31560387https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37379865Babies are born to breastfeed. While 50% of lactating persons struggle to make enough milk, there are no governmentally-approved drugs to enhance lactation. This dissertation the initial development of a long-lasting biologic to enhance milk supply as a potentially powerful pharmacologic means to combat lactation insufficiency. Chapter 2 describes our engineering strategies to design a long-acting prolactin to combat lactation insufficiency. Our engineered variant, Prolactin-eXtra Long-acting (Prolactin-XL), is comprised of endogenously active human prolactin fused to an engineered human IgG Fc domain designed to overcome the unique drug development challenges specific to the lactating person-infant dyad. In mouse studies, we show that Prolactin-XL has a long serum half-life and enhances lactation. This work expands the toolkit of protein engineering in drug development to design biologics. Chapter 3 consists of concluding remarks on the potential of Prolactin-XL to impact lactation insufficiency, sustainability, conservation, and mammary gland biology. This chapter also explores how antibody-based biologics can be designed to be compatible with both pregnancy and lactation to further expand the therapeutic toolkit available to pregnant and lactating patients.application/pdfenSystematic biologyBioengineeringThesis or Dissertation2024-11-200000-0001-6103-3672