RNA and protein-based therapeutics constitute almost half of recent drug approvals and receive considerable attention within biotechnology industries. Ensuring their stability and longevity in the context of heat, freezing, and lyophilization processes are paramount to a successful deployment. However, the advancement of formulations designed to achieve this goal is still in its nascent phase. To address these challenges, a new class of semi-dendritic hydrophilic polymer with extended linear units is reported, which showcase very high hydration. These novel polymers demonstrated exceptional efficacy in preserving messenger RNA- (mRNA-) and self-amplifying RNA- (saRNA-) lipid nanoparticles during freezing and lyophilization. Additionally, they have been found to protect therapeutic proteins against external stressors such as freezing, heat, and lyophilization. These polymers are non-toxic, which enables their utilization at high concentrations and eliminates the requirement for removal prior to administration. It is found that their unique topology contributes to the high hydration. These excipients are anticipated to create new prospects in biotechnology, food science, and cryopreservation.
