Therapeutic Approaches for the Management of Autoimmune Disorders via Gene Therapy: Prospects, Challenges, and Opportunities

2021 ◽  
Vol 21 ◽  
Author(s):  
Rakesh K. Sindhu ◽  
Piyush Madaan ◽  
Parteek Chandel ◽  
Rokeya Akter ◽  
G. Adilakshmi ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gene Therapy ◽  
Immune Response ◽  
Animal Models ◽  
Autoimmune Diseases ◽  
Animal Studies ◽  
Viral Vectors ◽  
Challenges And Opportunities ◽  
Organ Specific ◽  
Inflammatory Bowel

Background: Autoimmune diseases are the diseases that result due to the overactive immune response, and comprise systemic autoimmune diseases like rheumatoid arthritis (RA), sjӧgren’s syndrome (SS), and organ-specific autoimmune diseases like type-1 diabetes mellitus (T1DM), myasthenia gravis (MG), and inflammatory bowel disease (IBD). Currently, there is no long-term cure; but, several treatments exist which retard the evolution of the disease, embracing gene therapy, which has been scrutinized to hold immense aptitude for the management of autoimmune diseases. Objective: The review highlights the pathogenic mechanisms and genes liable for the development of autoimmune diseases, namely T1DM, type-2 diabetes mellitus (T2DM), RA, SS, IBD, and MG. Furthermore, the review focuses on investigating the outcomes of delivering the corrective genes with their specific viral vectors in various animal models experiencing these diseases to determine the effectiveness of gene therapy. Methods: Numerous review and research articles emphasizing the tremendous potential of gene therapy in the management of autoimmune diseases were procured from PubMed, MEDLINE, Frontier, and other databases and thoroughly studied for writing this review article. Results: The various animal models that experienced treatment with gene therapy have displayed regulation in the levels of proinflammatory cytokines, infiltration of lymphocytes, manifestations associated with autoimmune diseases, and maintained equilibrium in the immune response, thereby hinder the progression of autoimmune diseases. Conclusion: Gene therapy has revealed prodigious aptitude in the management of autoimmune diseases in various animal studies, but further investigation is essential to combat the limitations associated with it and before employing it on humans.

scholarly journals Role of Lipid-Based and Polymer-Based Non-Viral Vectors in Nucleic Acid Delivery for Next-Generation Gene Therapy

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2866 ◽  
Author(s):  
Aniket Wahane ◽  
Akaash Waghmode ◽  
Alexander Kapphahn ◽  
Karishma Dhuri ◽  
Anisha Gupta ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Nucleic Acid ◽  
Messenger Rna ◽  
Viral Vectors ◽  
Cationic Lipids ◽  
Nucleic Acid Delivery ◽  
Nucleic Acid Analogs ◽  
Organ Specific ◽  
Interfering Rna

The field of gene therapy has experienced an insurgence of attention for its widespread ability to regulate gene expression by targeting genomic DNA, messenger RNA, microRNA, and short-interfering RNA for treating malignant and non-malignant disorders. Numerous nucleic acid analogs have been developed to target coding or non-coding sequences of the human genome for gene regulation. However, broader clinical applications of nucleic acid analogs have been limited due to their poor cell or organ-specific delivery. To resolve these issues, non-viral vectors based on nanoparticles, liposomes, and polyplexes have been developed to date. This review is centered on non-viral vectors mainly comprising of cationic lipids and polymers for nucleic acid-based delivery for numerous gene therapy-based applications.

scholarly journals Intratracheal aerosolization of viral vectors to newborn pig airways

BioTechniques ◽  
2020 ◽  
Vol 68 (5) ◽  
pp. 235-239
Author(s):  
Ashley L Cooney ◽  
Patrick L Sinn
Keyword(s):  
Gene Therapy ◽  
Animal Models ◽  
Endotracheal Tube ◽  
Viral Vectors ◽  
Small Animal ◽  
Large Animal ◽  
Large Animal Models ◽  
Airway Diseases ◽  
Efficient Delivery ◽  
Large Animals

Gene therapy for airway diseases requires efficient delivery of nucleic acids to the airways. In small animal models, gene delivery reagents are commonly delivered as a bolus dose. However, large animal models are often more relevant for the transition from preclinical studies to human trials. Aerosolizing viral vectors to the lungs of large animals can maximize anatomical distribution. Here, we describe a technique for aerosolization of viral vectors to the airways of newborn pigs. Briefly, a pig is anesthetized and intubated with an endotracheal tube, and a microsprayer is passed through the endotracheal tube. A fine mist is then sprayed into the distal trachea. Widespread and uniform distribution of transgene expression is critical for developing successful lung gene therapy treatments.

scholarly journals Translational Potential of Metabolomics on Animal Models of Inflammatory Bowel Disease—A Systematic Critical Review

2020 ◽  
Vol 21 (11) ◽  
pp. 3856
Author(s):  
Lina Almind Knudsen ◽  
Rasmus Desdorf ◽  
Sören Möller ◽  
Signe Bek Sørensen ◽  
Axel Kornerup Hansen ◽  
...  
Keyword(s):  
Systematic Review ◽  
Inflammatory Bowel Disease ◽  
Animal Models ◽  
Bowel Disease ◽  
Animal Studies ◽  
Detection Methods ◽  
Sample Type ◽  
Key Factor ◽  
Inflammatory Bowel ◽  
Functional Relevance

In the development of inflammatory bowel disease (IBD), the gut microbiota has been established as a key factor. Recently, metabolomics has become important for understanding the functional relevance of gut microbial changes in disease. Animal models for IBD enable the study of factors involved in disease development. However, results from animal studies may not represent the human situation. The aim of this study was to investigate whether results from metabolomics studies on animal models for IBD were similar to those from studies on IBD patients. Medline and Embase were searched for relevant studies up to May 2017. The Covidence systematic review software was used for study screening, and quality assessment was conducted for all included studies. Data showed a convergence of ~17% for metabolites differentiated between IBD and controls in human and animal studies with amino acids being the most differentiated metabolite subclass. The acute dextran sodium sulfate model appeared as a good model for analysis of systemic metabolites in IBD, but analytical platform, age, and biological sample type did not show clear correlations with any significant metabolites. In conclusion, this systematic review highlights the variation in metabolomics results, and emphasizes the importance of expanding the applied detection methods to ensure greater coverage and convergence between the various different patient phenotypes and animal models of inflammatory bowel disease.

Gene therapy in autoimmune diseases: Challenges and opportunities

2010 ◽  
Vol 9 (3) ◽  
pp. 170-174 ◽  
Author(s):  
Patrick S.C. Leung ◽  
Amy Dhirapong ◽  
Ping-Yi Wu ◽  
Mi-Hua Tao
Keyword(s):  
Gene Therapy ◽  
Autoimmune Diseases ◽  
Challenges And Opportunities

Bisphenol A as a Factor in the Mosaic of Autoimmunity

2021 ◽  
Vol 21 ◽  
Author(s):  
Zora Lazurova ◽  
Ivica Lazurova ◽  
Yehuda Shoenfeld
Keyword(s):  
Bisphenol A ◽  
Autoimmune Diseases ◽  
Thyroid Autoimmunity ◽  
Diabetes Mellitus Type 1 ◽  
Systemic Autoimmune Diseases ◽  
Physiological Processes ◽  
Oncological Diseases ◽  
Organ Specific ◽  
Inflammatory Bowel

The population worldwide is largely exposed to bisphenol A (BPA), a commonly used plasticizer, that has a similar molecular structure to endogenous estrogens. Therefore, it is able to influence physiological processes in human body, taking part in the pathophysiology of various endocrinopathies, as well as, cardiovascular, neurological and oncological diseases. BPA has been found to affect the immune system, leading to the development of autoimmunity and allergies, too. In the last few decades, the prevalence of autoimmune diseases has significantly increased, that could be explained by a rising exposure of the population to environmental factors, such as BPA. BPA has been found to play a role in the pathogenesis of systemic autoimmune diseases and also organ-specific autoimmunity (thyroid autoimmunity, diabetes mellitus type 1, myocarditis, inflammatory bowel disease, multiple sclerosis, encephalomyelitis etc), but the results of some studies remain still controversial, so further research is needed.

Genetic Susceptibility to the Development of Autoimmune Disease

1997 ◽  
Vol 93 (6) ◽  
pp. 479-491 ◽  
Author(s):  
Joanne Heward ◽  
Stephen C. L. Gough
Keyword(s):  
Diabetes Mellitus ◽  
Autoimmune Diseases ◽  
Insulin Dependent Diabetes Mellitus ◽  
Population Based ◽  
Case Control ◽  
Insulin Dependent Diabetes ◽  
Dependent Diabetes Mellitus ◽  
Case Control Studies ◽  
Organ Specific ◽  
Insulin Dependent

1. Autoimmune diseases are common conditions which appear to develop in genetically susceptible individuals, with expression of disease being modified by permissive and protective environments. Familial clustering and data from twin studies provided the impetus for the search for putative loci. Both the candidate gene approach in population-based case-control studies and entire genome screening in families have helped identify susceptibility genes in a number of autoimmune diseases. 2. After the first genome screen in type 1 (insulin-dependent) diabetes mellitus it seems likely that most autoimmune diseases are polygenic with no single gene being either necessary or sufficient for disease development. Of the organ-specific autoimmune diseases, genome screens have now been completed in insulin-dependent diabetes mellitus and multiple sclerosis. Furthermore, the clustering of autoimmune diseases within the same individuals suggests that the same genes may be involved in the different diseases. This is supported by data showing that both HLA (human leucocyte antigen) and CTLA-4 (cytotoxic T-lymphocyte-associated-4) appear to be involved in the development of insulin-dependent diabetes mellitus and Graves' disease. 3. Genome screens have also been completed in some of the non-organ-specific autoimmune diseases including rheumatoid arthritis, inflammatory bowel disease and psoriasis. Many candidate genes have also been investigated although these are predominantly in population-based case-control studies. 4. Substantial progress has been made in recent years towards the identification of susceptibility loci in autoimmune diseases. The inconsistencies seen between case-control studies may largely be due to genetic mismatching between cases and controls in small datasets. Family-based association studies are being increasingly used to confirm genetic linkages and help with fine mapping strategies. It will, however, require a combination of biology and genetics, as has been necessary with the major histocompatibility complex in insulin-dependent diabetes mellitus, to identify primary aetiological mutations.

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