Polycation-based nanoparticle delivery of RNAi therapeutics: adverse effects and solutions.

Abstract:

:Small interfering RNA (siRNA) that silence genes by the process of RNA interference offers a new therapeutic modality for disease treatment. Polycation-based nanoparticles termed polyplexes have been developed to maximise extracellular and intracellular siRNA delivery, a key requirement for enabling the clinical translation of RNAi-based drugs. Medical applications are dependent on safety; therefore, detailed investigation into potential toxicity to the cell or organism is required. This review addresses potential adverse effects arising from cellular and tissue interactions, immune stimulation and altered gene expression that can be associated with the assembled polyplex or the polycation and siRNA component parts. A greater understanding of the cellular mechanisms involved allows design-based solutions for rationale development of safe, effective and clinically relevant polyplex-based RNAi drugs.

journal_name

Adv Drug Deliv Rev

authors

Ballarín-González B,Howard KA

doi

10.1016/j.addr.2012.07.004

subject

Has Abstract

pub_date

2012-12-01 00:00:00

pages

1717-29

issue

15

eissn

0169-409X

issn

1872-8294

pii

S0169-409X(12)00223-2

journal_volume

64

pub_type

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