RNAi therapeutics: SNALPing siRNAs in vivo

  title={RNAi therapeutics: SNALPing siRNAs in vivo},
  author={John J. Rossi},
  journal={Gene Therapy},
  • J. Rossi
  • Published 1 April 2006
  • Biology, Medicine
  • Gene Therapy
The novel use of a lipid bilayer system to get fusogenic delivery of siRNAs to murine liver cells to inhibit replication of the Hepatitis B virus (HBV) is the latest in a series of studies that address the major problem that faces RNAi therapeutics: delivering the RNAi agents to where they can make a difference. 
Author Correction: Intranasal drug delivery of small interfering RNA targeting Beclin1 encapsulated with polyethylenimine (PEI) in mouse brain to achieve HIV attenuation
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Advances in siRNA delivery in cancer therapy
The barriers, potential siRNA drug delivery systems, and application of siRNA in clinical trials for cancer therapy are reviewed to harness the full potential of si RNA as a cancer therapeutic.
Insight Into the Prospects for RNAi Therapy of Cancer
The role ofRNAi in the treatment of COVID-19, the novel coronavirus disease plaguing many countries, has been discussed and the current challenges of RNAi therapy are explored by identifying some of the cancer delivery systems and providing drug information for their improvement.
Nanotoxicity: a key obstacle to clinical translation of siRNA-based nanomedicine.
The nanotoxicity of siRNA carriers is reviewed to help clear the way for siRNAs to fulfill their promise as a versatile class of therapeutic agents.
Preclinical development of siRNA therapeutics: towards the match between fundamental science and engineered systems.
This review discusses recent progress and pertinent limiting factors related to the use of siRNA-s as efficient protein-specific "silencing" agents, focusing on targeted delivery not only to cells of interest, but to the proper intracellular destination.
Nanoparticle-Based Delivery of RNAi Therapeutics: Progress and Challenges
The major hurdles in achieving efficient RNAi delivery are introduced and the current advances in applying nanotechnology-based delivery systems to overcome the delivery hurdles of RNAi therapeutics are discussed.
RNAi-mediated inhibition of the glucosylceramide synthase (GCS) gene: A preliminary study towards a therapeutic strategy for Gaucher disease and other glycosphingolipid storage diseases.
A new approach based on the inhibition of the GCS gene using siRNAs as a potential therapeutic strategy for Gaucher disease is presented and a clear reduction of GCS RNA levels and enzyme activity was obtained using two of the four siRN as well as a reduction in glucosylceramide synthesis.
Development of RNAi technology for targeted therapy--a track of siRNA based agents to RNAi therapeutics.
In this review, it is summarized that barriers exist in the delivery process and popular functionalized technologies for siRNA such as chemical modification and physical encapsulation and the future of siRNA delivery was proposed.
Lipids and Lipid Derivatives for RNA Delivery.
Recent advances of lipids, lipid derivatives, and lipid-derived macromolecules used in RNA delivery over the past several decades are covered, mainly on their chemical structures, synthetic routes, characterization, formulation methods, and structure-activity relationships.
Delivering the right message: Challenges and opportunities in lipid nanoparticles-mediated modified mRNA therapeutics-An innate immune system standpoint.
The main factors, which determine the fate of modified mRNA (mmRNA)-loaded LNPs in-vivo, are discussed, and will focus on their interactions with the innate immune system as a main consideration in the design of lipid-based mmRNA delivery platforms.


Cationic lipids enhance siRNA-mediated interferon response in mice.
It is shown that although intravenous administration of siRNA alone is essentially inert, injection of si RNA complexed with cationic liposomes resulted in a potent induction of both type I and type II interferon responses.
Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs
The advances demonstrated here, including persistence of in vivo activity, use of lower doses and reduced dosing frequency are important steps in making siRNA a clinically viable therapeutic approach.
Activity of stabilized short interfering RNA in a mouse model of hepatitis B virus replication
These experiments establish the strong impact that siRNAs can have on the extent of HBV infection and underscore the importance of stabilization of siRNA against nuclease degradation.
Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs
It is shown that chemically modified short interfering RNAs (siRNAs) can silence an endogenous gene encoding apolipoprotein B (apoB) after intravenous injection in mice, and it is determined that cleavage of the apoB mRNA occurred specifically at the predicted site.
Sequence-dependent stimulation of the mammalian innate immune response by synthetic siRNA
It is reported that synthetic siRNAs formulated in nonviral delivery vehicles can be potent inducers of interferons and inflammatory cytokines both in vivo in mice and in vitro in human blood.
Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors
The potential for systemic, cell-type specific, antibody-mediated siRNA delivery to HIV-infected or envelope-transfected cells is demonstrated and an ErbB2 single-chain antibody fused with protamine delivered siRNAs specifically into ErBB2-expressing cancer cells.
Specific inhibition of gene expression by small double-stranded RNAs in invertebrate and vertebrate systems
Synthetic siRNAs can induce gene-specific inhibition of expression in Caenorhabditis elegans and in cell lines from humans and mice, and seem to avoid the well documented nonspecific effects triggered by longer double-stranded RNAs in mammalian cells.
Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
21-nucleotide siRNA duplexes provide a new tool for studying gene function in mammalian cells and may eventually be used as gene-specific therapeutics.
Sequence-specific potent induction of IFN-α by short interfering RNA in plasmacytoid dendritic cells through TLR7
Injection into mice of immunostimulatory siRNA, when complexed with cationic liposomes, induced systemic immune responses in the same range as the TLR9 ligand CpG, including IFN-α in serum and activation of T cells and dendritic cells in spleen.
Induction of Inflammatory Cytokines by Double- stranded and Single-stranded siRNAs is Sequence- dependent and Requires Endosomal Localization
YJMBI 57125—21/3/2005—17:11—SFORSTER 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 RE CT ED P RO OF The potential induction of inflammatory