Charge-alteration-based approaches can address the evolving needs of nucleic acid-based gene therapy, charge reversal techniques are also promising

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Gene Therapy ◽  
Nucleic Acid ◽  
Early Development ◽  
Disease Models ◽  
Charge Reversal ◽  
Delivery Vector ◽  
Medication Delivery ◽  
Development Phases ◽  
Therapeutic Platform ◽  
Positively Charged

Recent approvals of RNAi-based medications have rekindled interest in the industry, possibly strengthening the power of the therapeutic platform. Many groundbreaking research endeavors have offered new carrier architectures for carrying nucleic acid payloads. Because nucleic acids are charged negatively, utilizing complementary positively charged compounds sounds like a smart approach. The presence of such a cationic charge in the delivery vector, however, is a serious problem, increasing cytotoxicity. Charge-alteration-based approaches can address the evolving needs of nucleic acid-based therapies. Medication delivery platforms have become significantly smarter and safer.The research focuses on exciting recent advancements in management-switching technology. This study summarizes some of these fascinating possibilities, written by authors with special attention to the underlying physics of charge conversion processes. Charge reversal techniques are fairly new and are still in the early development phases. Translating such ideas would require significant investigation, including studies of safety, efficacy, and immunogenicity using relevant disease models.

scholarly journals Effective lung-targeted RNAi in mice with peptide-based delivery of nucleic acid

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kaido Kurrikoff ◽  
Krista Freimann ◽  
Kadi-Liis Veiman ◽  
Elin Madli Peets ◽  
Andres Piirsoo ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Nucleic Acid ◽  
Lung Disease ◽  
Lung Tissue ◽  
Lung Inflammation ◽  
Disease Models ◽  
Nucleic Acid Delivery ◽  
Acute Lung Inflammation ◽  
Disease Symptoms ◽  
Targeted Gene Therapy

AbstractWe have previously developed efficient peptide-based nucleic acid delivery vectors PF14 and NF55, where we have shown that these vectors preferentially transfect lung tissue upon systemic administration with the nucleic acid. In the current work, we have explored the utilization and potential of these vectors for the lung-targeted gene therapy. Accordingly, we assessed the efficacy of these peptides in (i) two different lung disease models – acute lung inflammation and asthma in mice and (ii) using two different nucleic acid cargos – siRNA and pDNA encoding shRNA. Using RNAi against cytokine TNFα, we showed efficient anti-inflammatory effects in both disease models and observed decreased disease symptoms. Our results highlight the potential of our transfection vectors for lung gene therapy.

Evaluation of the nucleopolyhedrovirus of Anticarsia gemmatalis as a vector for gene therapy in mammals

2020 ◽  
Vol 20 ◽  
Author(s):  
Cintia N. Parsza ◽  
Diego L. Mengual Gómez ◽  
Jorge Alejandro Simonin ◽  
Mariano Nicolás Belaich ◽  
Pablo Daniel Ghiringhelli
Keyword(s):  
Gene Therapy ◽  
Mammalian Cells ◽  
Insect Cells ◽  
Autographa Californica ◽  
Anticarsia Gemmatalis ◽  
Agricultural Pests ◽  
Mammalian Cell Lines ◽  
Delivery Vector ◽  
Wide Range ◽  
Insect Pathogens

Background: Baculoviruses are insect pathogens with important biotechnological applications that transcend their use as biological controllers of agricultural pests. One species, Autographa californica multiple nucleopolhyedrovirus (AcMNPV) has been extensively exploited as a molecular platform to produce recombinant proteins and as a delivery vector for genes in mammals, because it can transduce a wide range of mammalian cells and tissues without replicating or producing progeny. Objective/Method: To investigate if the budded virions of Anticarsia gemmatalis multiple nucleopolhyedrovirus (AgMNPV) species has the same ability, the viral genome was modified by homologous recombination into susceptible insect cells to integrate reporter genes and then it was evaluated on mammalian cell lines in comparative form with respect to equivalent viruses derived from AcMNPV. Besides, the replicative capacity of AgMNPV´s virions in mammals was determined. Results: The experiments carried out showed that the recombinant variant of AgMNPV transduces and support the expression of delivered genes but not replicates in mammalian cells. Conclusion: Consequently, this insect pathogen is proposed as an alternative of non-infectious viruses in humans to explore new approaches in gene therapy and other applications based on the use of mammalian cells.

Exosome as a Natural Gene Delivery Vector for Cancer Treatment

2020 ◽  
Vol 20 (11) ◽  
pp. 821-830
Author(s):  
Prasad Pofali ◽  
Adrita Mondal ◽  
Vaishali Londhe
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Nucleic Acids ◽  
Cancer Treatment ◽  
Intestinal Barrier ◽  
Gene Carrier ◽  
Gene Delivery Vector ◽  
Delivery Vector

Background: Current gene therapy vectors such as viral, non-viral, and bacterial vectors, which are used for cancer treatment, but there are certain safety concerns and stability issues of these conventional vectors. Exosomes are the vesicles of size 40-100 nm secreted from multivesicular bodies into the extracellular environment by most of the cell types in-vivo and in-vitro. As a natural nanocarrier, exosomes are immunologically inert, biocompatible, and can cross biological barriers like the blood-brain barrier, intestinal barrier, and placental barrier. Objective: This review focusses on the role of exosome as a carrier to efficiently deliver a gene for cancer treatment and diagnosis. The methods for loading of nucleic acids onto the exosomes, advantages of exosomes as a smart intercellular shuttle for gene delivery and therapeutic applications as a gene delivery vector for siRNA, miRNA and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and also the limitations of exosomes as a gene carrier are all reviewed in this article. Methods: Mostly, electroporation and chemical transfection are used to prepare gene loaded exosomes. Results: Exosome-mediated delivery is highly promising and advantageous in comparison to the current delivery methods for systemic gene therapy. Targeted exosomes, loaded with therapeutic nucleic acids, can efficiently promote the reduction of tumor proliferation without any adverse effects. Conclusion: In the near future, exosomes can become an efficient gene carrier for delivery and a biomarker for the diagnosis and treatment of cancer.

Nucleic acid-based antiviral and gene therapy of chronic hepatitis B infection

1997 ◽  
Vol 12 (9-10) ◽  
pp. S354-S369 ◽  
Author(s):  
JR WANDS ◽  
M GEISSLER ◽  
JZU PUTLITZ ◽  
H BLUM ◽  
F WEIZSÄCKER ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Chronic Hepatitis ◽  
Nucleic Acid ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Hepatitis B Infection ◽  
Chronic Hepatitis B Infection

I.—On the Developmental Processes in Mammary Glands and other Epidermal Structures

1952 ◽  
Vol 62 (1) ◽  
pp. 1-31 ◽  
Author(s):  
B. I. Balinsky
Keyword(s):  
Alkaline Phosphatase ◽  
Nucleic Acid ◽  
Early Development ◽  
Mammary Glands ◽  
Mitotic Rate ◽  
Hair Follicles ◽  
Developmental Processes ◽  
Histochemical Methods

Synopsis:The early development of the mammary glands and of hair follicles in the mouse and the rabbit has been investigated by means of mitotic counts, by histochemical methods and by cultivation in vitro. In the first stage of the formation of both types of rudiment a thickening of the epidermis appears as a consequence of an aggregation of cells, not of a local elevation of the mitotic rate. During this stage alkaline phosphatase is absent from the cells and the content of ribose-nucleic acid reduced. Both these substances appear in higher concentrations later, and their relation to processes of growth and differentiation is discussed. Essentially similar phenomena are found in rudiments cultivated in vitro, which, however, frequently suffer a degeneration by a process of keratinisation.

Unlockable Nanocomplexes with Self-Accelerating Nucleic Acid Release for Effective Staged Gene Therapy of Cardiovascular Diseases

2018 ◽  
Vol 30 (31) ◽  
pp. 1801570 ◽  
Author(s):  
Jing-Jun Nie ◽  
Bokang Qiao ◽  
Shun Duan ◽  
Chen Xu ◽  
Boya Chen ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Nucleic Acid ◽  
Cardiovascular Diseases ◽  
Acid Release

Gene therapy promises accurate, targeted administration and overcoming drug resistance in diverse cancer cells

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Gene Therapy ◽  
Drug Resistance ◽  
Nucleic Acid ◽  
Nucleic Acids ◽  
Clinical Research ◽  
Cancer Cells ◽  
Cationic Lipids ◽  
Target Cells ◽  
Genetic Components ◽  
Wide Range

Nucleic acid-based therapeutics such as siRNA and miRNA employ the silencing capabilities of the RNAi mechanism to affect the expression of one gene or several genes in target cells. Nucleic acid-based therapies enable accurate, targeted administration and overcoming drug resistance in diverse cancer cells. Several studies have shown that they can be utilized alongside pharmacological therapy to increase the efficacy of existing therapies. In addition, nucleic acid-based therapies have the potential to widen the spectrum of druggable targets for a range of diseases and emerge as a novel therapeutic technique for treating a number of diseases that are today untreatable. Nucleic acids are dependent on their effective distribution to target cells, which need correct complexation and encapsulation in a delivery mechanism. Although nucleic acids exist in a variety of forms and sizes, their physical and chemical commonality allow them to be loaded into a wide range of delivery vehicles. The primary biomaterials used to encapsulate genetic components were cationic lipids and polymers. Furthermore, the experiments focused particularly on effective transfection in target cells.Recent breakthroughs in NP-based RNA therapeutics have spurred a flood of clinical research, facing many challenges. In vivo, pharmacokinetics of different RNA-based medications must be researched to establish the viability and therapeutic potential of nucleic acid-based therapeutics. The U.S. Food and Drug Administration recently authorized many NP-based gene therapy. In 2019, Novartis authorized Zolgensma (onasemnogene abeparvovec-xioi) to treat spinal muscle atrophy. The first clinical research employing siRNA began in 2004 and is considered a milestone in nucleic acid-based drug development. Thirty clinical investigations have subsequently been completed. In 2018, the US FDA cleared Onpattro (Patisiran, Alnylam Pharmaceuticals) for the treatment of polyneuropathy caused by transthyretin amyloidosis.Several new generations of nucleic acid compositions employing polymer nanoparticles or liposomes are presently undergoing clinical testing. If allowed, the debut of nucleic acid-based treatments would represent a watershed event in immunotherapy. Advances in the design and development of biocompatible nanomaterials would allow us to overcome the above-mentioned problems and so show the potential to deliver nucleic acids in the treatment of a number of illnesses.

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