TY - JOUR

T1 - Engineering aspects of lipid-based delivery systems

T2 - In vivo gene delivery, safety criteria, and translation strategies

AU - Eş, Ismail

AU - Thakur, Aneesh

AU - Mousavi Khaneghah, Amin

AU - Foged, Camilla

AU - de la Torre, Lucimara Gaziola

N1 - Copyright © 2024 Elsevier Inc. All rights reserved.

PY - 2024

Y1 - 2024

N2 - Defects in the genome cause genetic diseases and can be treated with gene therapy. Due to the limitations encountered in gene delivery, lipid-based supramolecular colloidal materials have emerged as promising gene carrier systems. In their non-functionalized form, lipid nanoparticles often demonstrate lower transgene expression efficiency, leading to suboptimal therapeutic outcomes, specifically through reduced percentages of cells expressing the transgene. Due to chemically active substituents, the engineering of delivery systems for genetic drugs with specific chemical ligands steps forward as an innovative strategy to tackle the drawbacks and enhance their therapeutic efficacy. Despite intense investigations into functionalization strategies, the clinical outcome of such therapies still needs to be improved. Here, we highlight and comprehensively review engineering aspects for functionalizing lipid-based delivery systems and their therapeutic efficacy for developing novel genetic cargoes to provide a full snapshot of the translation from the bench to the clinics. We outline existing challenges in the delivery and internalization processes and narrate recent advances in the functionalization of lipid-based delivery systems for nucleic acids to enhance their therapeutic efficacy and safety. Moreover, we address clinical trials using these vectors to expand their clinical use and principal safety concerns.

AB - Defects in the genome cause genetic diseases and can be treated with gene therapy. Due to the limitations encountered in gene delivery, lipid-based supramolecular colloidal materials have emerged as promising gene carrier systems. In their non-functionalized form, lipid nanoparticles often demonstrate lower transgene expression efficiency, leading to suboptimal therapeutic outcomes, specifically through reduced percentages of cells expressing the transgene. Due to chemically active substituents, the engineering of delivery systems for genetic drugs with specific chemical ligands steps forward as an innovative strategy to tackle the drawbacks and enhance their therapeutic efficacy. Despite intense investigations into functionalization strategies, the clinical outcome of such therapies still needs to be improved. Here, we highlight and comprehensively review engineering aspects for functionalizing lipid-based delivery systems and their therapeutic efficacy for developing novel genetic cargoes to provide a full snapshot of the translation from the bench to the clinics. We outline existing challenges in the delivery and internalization processes and narrate recent advances in the functionalization of lipid-based delivery systems for nucleic acids to enhance their therapeutic efficacy and safety. Moreover, we address clinical trials using these vectors to expand their clinical use and principal safety concerns.

KW - Gene delivery

KW - Gene therapy

KW - Lipid-based delivery system

KW - Non-viral vectors

KW - Surface functionalization

U2 - 10.1016/j.biotechadv.2024.108342

DO - 10.1016/j.biotechadv.2024.108342

M3 - Review

C2 - 38518964

VL - 72

JO - Biotechnology Advances

JF - Biotechnology Advances

SN - 0734-9750

M1 - 108342

ER -