Abstract: The present disclosure relates to pharmaceutical compositions comprising a lipid nanoparticle (LNP), a therapeutic nucleic acid (TNA) and at least one pharmaceutically acceptable excipient, wherein the LNP comprises at least one lipid, and wherein the LNP is capable of delivering the TNA to a retinal cell. Methods of treating ocular diseases and disorders are also provided.

Abstract: Provided herein are pharmaceutical compositions comprising a lipid nanoparticle (LNP) and a therapeutic nucleic acid (TNA), wherein the LNP comprises an ApoE polypeptide, or a fragment thereof and/or an ApoB polypeptide, or a fragment thereof, linked to the LNP, and at least one pharmaceutically acceptable excipient. The ApoE polypeptide, or the fragment thereof, and/or the ApoB polypeptide, or the fragment thereof, are capable of binding a low-density lipoprotein (LDL) receptor, or LDL receptor family member, advantageously providing LNP compositions that can be directed to any cell or tissue expressing the LDL receptor.

Abstract: Provided herein are lipid formulations of reduced size, comprising a lipid and a capsid free, non-viral vector (e.g., ceDNA), and methods of producing said lipid formulations. Lipid particles (e.g., lipid nanoparticles) of the disclosure include a lipid formulation that can be used to deliver a capsid-free, non-viral DNA vector to a target site of interest (e.g., cell, tissue, organ, and the like).

Abstract: Provided herein are ionizable lipids represented by the Formula (I): or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, R6, R1?, R2?, R3?, R4?, R5?, R6?, m, and n are as defined herein. Also provided herein are lipid nanoparticle (LNP) compositions comprising an ionizable lipid of the invention and a capsid-free, non-viral vector (e.g., ceDNA). These LNPs can be used to deliver a capsid-free, non-viral DNA vector to a target site of interest (e.g., cell, tissue, organ, and the like).