Emerging lipid-polymer hybrid nanoparticles for genome editing

Genome editing technologies have been key to unlocking new bioengineering strategies as they enable the modification of mammalian cells' genes in a fully user-programmed mode. Despite major advancements, the development of proficient systems for a safer and more efficient delivery of gene editing machineries into all classes of mammalian cells is still challenging. In this context, new generations of lipid-polymer hybrid nanoparticles are rapidly emerging as potentially valuable alternatives to upgrade mainstream gene delivery toolboxes. Building on this, herein we showcase the most recent advances in designing hybrid nanocarriers for the delivery of genome editing components. Major polymer and lipid features harnessed for optimal CRISPR/Cas9-based gene editing, along with tissue- and cell-targeting strategies are specifically highlighted. Alongside this, key technologies for the formulation of lipid-polymer conjugates are showcased. Such hybrid vehicles, along with the existing chemical toolsets are envisioned to unlock progressively more proficient nonviral platforms for maximizing genome editing efficacy, especially in the most challenging primary cells or tissues. Lipid-polymer hybrid nanoparticles are rapidly emerging as a major class of efficient delivery systems for biomedical applications. This review showcases and discusses the designs and major advances of lipid-polymer hybrids for genome editing strategies.