TY - JOUR

T1 - Complexity in the therapeutic delivery of RNAi medicines

T2 - an analytical challenge

AU - Colombo, Stefano

AU - Zeng, Xianghui

AU - Ragelle, Héloïse

AU - Foged, Camilla

PY - 2014/9

Y1 - 2014/9

N2 - INTRODUCTION: Nucleic acids have witnessed a dramatic acceleration in their therapeutic exploitation and currently represent a growing number of applications in drug development pipelines. However, a more wide-spread development of therapeutics based on nucleic acids is restricted by their poor chemical and enzymatic stability in vivo, lack of cellular uptake and insufficient capability to reach intracellular targets.AREAS COVERED: Advanced formulation of nucleic acids in nano-sized carriers may help unlocking their potential as therapeutic agents. Nano-sized matters own specific features responsible for inducing characteristic interactions with biological molecules and tissues. These properties enable for the enhancement of the nano-formulation's therapeutic efficacy, but on the other hand, the nanomatters interactions in biological fluids are also responsible for adverse effects. The purpose of this review is to reflect on the complexity in the therapeutic delivery of RNA interference-based drugs emerging from the recent clinical experiences and report the actual technological and analytical advances introduced to solve it.EXPERT OPINION: The complexity in the therapeutic delivery of nucleic acids and the heterogeneity of side effects make the interpretation of the therapeutic outcome difficult. Hence the development of analytical approaches applicable in the field of nucleic acid delivery is becoming a major challenge.

AB - INTRODUCTION: Nucleic acids have witnessed a dramatic acceleration in their therapeutic exploitation and currently represent a growing number of applications in drug development pipelines. However, a more wide-spread development of therapeutics based on nucleic acids is restricted by their poor chemical and enzymatic stability in vivo, lack of cellular uptake and insufficient capability to reach intracellular targets.AREAS COVERED: Advanced formulation of nucleic acids in nano-sized carriers may help unlocking their potential as therapeutic agents. Nano-sized matters own specific features responsible for inducing characteristic interactions with biological molecules and tissues. These properties enable for the enhancement of the nano-formulation's therapeutic efficacy, but on the other hand, the nanomatters interactions in biological fluids are also responsible for adverse effects. The purpose of this review is to reflect on the complexity in the therapeutic delivery of RNA interference-based drugs emerging from the recent clinical experiences and report the actual technological and analytical advances introduced to solve it.EXPERT OPINION: The complexity in the therapeutic delivery of nucleic acids and the heterogeneity of side effects make the interpretation of the therapeutic outcome difficult. Hence the development of analytical approaches applicable in the field of nucleic acid delivery is becoming a major challenge.

U2 - 10.1517/17425247.2014.927439

DO - 10.1517/17425247.2014.927439

M3 - Journal article

C2 - 24950005

VL - 11

SP - 1481

EP - 1495

JO - Expert Opinion on Drug Delivery

JF - Expert Opinion on Drug Delivery

SN - 1742-5247

IS - 9

ER -