Tissue-specific gene delivery approaches

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

For genetic therapies to have their intended benefit, delivery systems must be designed which reach disease-affected organs with high efficiency. To accomplish this, gene delivery systems must overcome multiple intra- and extracellular barriers to avoid rapid clearance from the body and/or significant accumulation in off-target sites which can lead to undesired side effects (e.g., genotoxicity, immunogenicity). This requires an in-depth knowledge of biomolecular and biophysical interactions at the nano-bio interface to engineer gene vectors which preferentially access specific organs such as the liver, spleen, and brain after systemic administration. In this review, we will discuss the strategies employed to engineer genetic therapies which selectively target organs of interest after systemic administration. We focus on three major classes of nucleic acid delivery systems including adeno-associated viruses, lipid nanoparticles, and polymeric nanoparticles (PNPs) which are all being explored for tissue-specific gene delivery. We will go on to describe how new, highly efficient adeno-associated virus variants as well as engineered lipid and PNPs can be discovered or rationally designed. We also discuss high throughput approaches for screening of these systems to establish important structure-to-function relationships that determine the fate of these gene delivery systems once adm

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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