Abstract
Short interfering RNAs (siRNAs) are the most commonly used RNA interference (RNAi) triggers. They hold promise as potent therapeutic tools, as demonstrated by recent successful in vivo experiments. However, in addition to triggering intended sequence-specific silencing effects, the reagents of RNAi technology can often cause side effects, including immunological off-target effects. The cellular sensors of foreign RNA, such as RIG-I or Toll-like receptors, involved in innate immune antiviral responses, are activated by RNAi reagents. Stimulation of these pathways results in changes in the cellular transcriptome and proteome that can lead to the inhibition of cell division and growth and eventually apoptosis. An additional undesired effect in the context of research applications may be the misinterpretation of experimental results. To date, a number of the specific features of siRNA structure, sequence and delivery mode that are responsible for these effects have been identified. This knowledge may be helpful in designing safer gene-silencing reagents. In this article we discuss the recent developments in the field of non-specific toxic effects caused by RNAi triggers and their delivery vehicles. These data are critically discussed and evaluated, taking advantage of relevant information compiled in the recently launched RNAimmuno database (http://rnaimmuno.ibch.poznan.pl).
Keywords: Interferon response, non-specific effects, RNAimmuno, RNA interference, siRNA, toxic effects
Current Gene Therapy
Title: Recent Advances in Understanding of the Immunological Off-Target Effects of siRNA
Volume: 11 Issue: 6
Author(s): Marta Olejniczak, Katarzyna Polak, Paulina Galka-Marciniak and Wlodzimierz J. Krzyzosiak
Affiliation:
Keywords: Interferon response, non-specific effects, RNAimmuno, RNA interference, siRNA, toxic effects
Abstract: Short interfering RNAs (siRNAs) are the most commonly used RNA interference (RNAi) triggers. They hold promise as potent therapeutic tools, as demonstrated by recent successful in vivo experiments. However, in addition to triggering intended sequence-specific silencing effects, the reagents of RNAi technology can often cause side effects, including immunological off-target effects. The cellular sensors of foreign RNA, such as RIG-I or Toll-like receptors, involved in innate immune antiviral responses, are activated by RNAi reagents. Stimulation of these pathways results in changes in the cellular transcriptome and proteome that can lead to the inhibition of cell division and growth and eventually apoptosis. An additional undesired effect in the context of research applications may be the misinterpretation of experimental results. To date, a number of the specific features of siRNA structure, sequence and delivery mode that are responsible for these effects have been identified. This knowledge may be helpful in designing safer gene-silencing reagents. In this article we discuss the recent developments in the field of non-specific toxic effects caused by RNAi triggers and their delivery vehicles. These data are critically discussed and evaluated, taking advantage of relevant information compiled in the recently launched RNAimmuno database (http://rnaimmuno.ibch.poznan.pl).
Export Options
About this article
Cite this article as:
Olejniczak Marta, Polak Katarzyna, Galka-Marciniak Paulina and J. Krzyzosiak Wlodzimierz, Recent Advances in Understanding of the Immunological Off-Target Effects of siRNA, Current Gene Therapy 2011; 11 (6) . https://dx.doi.org/10.2174/156652311798192770
DOI https://dx.doi.org/10.2174/156652311798192770 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
Call for Papers in Thematic Issues
Programmed Cell Death Genes in Oncology: Pioneering Therapeutic and Diagnostic Frontiers (BMS-CGT-2024-HT-45)
Programmed Cell Death (PCD) is recognized as a pivotal biological mechanism with far-reaching effects in the realm of cancer therapy. This complex process encompasses a variety of cell death modalities, including apoptosis, autophagic cell death, pyroptosis, and ferroptosis, each of which contributes to the intricate landscape of cancer development and ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Biological Therapy of Hematologic Malignancies: Toward a Chemotherapy- free Era
Current Medicinal Chemistry Effects of Green Tea on Iron Accumulation and Oxidative Stress in Livers of Iron-Challenged Thalassemic Mice
Medicinal Chemistry Hypertension to Heart Failure: New Developmental Strategies do not Cross a Clinical and Therapeutic Divide
Current Pharmaceutical Design Preface
Current Pharmaceutical Design Methotrexate Hepatotoxicity in Children with Juvenile Idiopathic Arthritis: A Single-Center Study
Current Rheumatology Reviews Gastrin-Releasing Peptide as a Molecular Target for Inflammatory Diseases: An Update
Inflammation & Allergy - Drug Targets (Discontinued) Claims of Current Inhaled Corticosteroid Patents for Treating Asthma
Recent Patents on Inflammation & Allergy Drug Discovery Prostaglandin E2: From Clinical Applications to Its Potential Role in Bone- Muscle Crosstalk and Myogenic Differentiation
Recent Patents on Biotechnology Natural Killer T Cells as Targets for Therapeutic Intervention in Autoimmune Diseases
Current Pharmaceutical Design Polymyxin-B Endotoxin Removal Device: Making the Point on Mechanisms of Action, Clinical Effectiveness and Possible Future Applications: Review
Infectious Disorders - Drug Targets miR-122 is a Unique Molecule with Great Potential in Diagnosis, Prognosis of Liver Disease, and Therapy Both as miRNA Mimic and Antimir
Current Gene Therapy The Use of Herbal Medicine in Cancer-related Anorexia/ Cachexia Treatment Around the World
Current Pharmaceutical Design Functional Roles of the Ca2+-activated K+ Channel, KCa3.1, in Brain Tumors
Current Neuropharmacology Altered Hyaluronan Biosynthesis and Cancer Progression: an Immunological Perspective
Mini-Reviews in Medicinal Chemistry OPLS-DA as a Suitable Method for Selecting a Set of Gene Transcripts Discriminating RAS- and PTPN11-Mutated Cells in Acute Lymphoblastic Leukaemia
Combinatorial Chemistry & High Throughput Screening Immune Abnormalities and Endotoxemia in Patients with Ulcerative Colitis and in Their First Degree Relatives: Attempts at Neutralizing Endotoxin- Mediated Effects
Current Pharmaceutical Design Pharmacokinetics of Selegiline in a Rabbit Model
Letters in Drug Design & Discovery Molecular and Cellular Mechanisms of Hexavalent Chromium-Induced Lung Cancer: An Updated Perspective
Current Drug Metabolism Targeting Ras Activity Prevented Amyloid Beta-Induced Aberrant Neuronal Cell Cycle Re-Entry and Death
Current Alzheimer Research The Effects of Ionic Gelation- Vibrational Jet Flow Technique in Fabrication of Microcapsules Incorporating β-cell: Applications in Diabetes
Current Diabetes Reviews