scholarly journals Chitosan-Based Drug Delivery System: Applications in Fish Biotechnology

Polymers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1177 ◽  
Author(s):  
Yuanbing Wu ◽  
Ania Rashidpour ◽  
María Pilar Almajano ◽  
Isidoro Metón
Keyword(s):  
Drug Delivery ◽  
Gene Therapy ◽  
Nucleic Acid ◽  
Gene Delivery ◽  
Gonadal Development ◽  
Endosomal Escape ◽  
Cell Uptake ◽  
Nucleic Acid Delivery ◽  
Farmed Fish ◽  
Therapy Studies

Chitosan is increasingly used for safe nucleic acid delivery in gene therapy studies, due to well-known properties such as bioadhesion, low toxicity, biodegradability and biocompatibility. Furthermore, chitosan derivatization can be easily performed to improve the solubility and stability of chitosan–nucleic acid polyplexes, and enhance efficient target cell drug delivery, cell uptake, intracellular endosomal escape, unpacking and nuclear import of expression plasmids. As in other fields, chitosan is a promising drug delivery vector with great potential for the fish farming industry. This review highlights state-of-the-art assays using chitosan-based methodologies for delivering nucleic acids into cells, and focuses attention on recent advances in chitosan-mediated gene delivery for fish biotechnology applications. The efficiency of chitosan for gene therapy studies in fish biotechnology is discussed in fields such as fish vaccination against bacterial and viral infection, control of gonadal development and gene overexpression and silencing for overcoming metabolic limitations, such as dependence on protein-rich diets and the low glucose tolerance of farmed fish. Finally, challenges and perspectives on the future developments of chitosan-based gene delivery in fish are also discussed.

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 Efficient Transfection of Large Plasmids Encoding HIV-1 into Human Cells—A High Potential Transfection System Based on a Peptide Mimicking Cationic Lipid

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 805
Author(s):  
Christopher Janich ◽  
Daniel Ivanusic ◽  
Julia Giselbrecht ◽  
Elena Janich ◽  
Shashank Reddy Pinnapireddy ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Plasma Membrane ◽  
Green Fluorescent Protein ◽  
Nucleic Acid ◽  
Fluorescent Protein ◽  
Cationic Lipid ◽  
Nucleic Acid Delivery ◽  
Molecular Clone ◽  
Green Fluorescent ◽  
Hiv 1

One major disadvantage of nucleic acid delivery systems is the low transfection or transduction efficiency of large-sized plasmids into cells. In this communication, we demonstrate the efficient transfection of a 15.5 kb green fluorescent protein (GFP)-fused HIV-1 molecular clone with a nucleic acid delivery system prepared from the highly potent peptide-mimicking cationic lipid OH4 in a mixture with the phospholipid DOPE (co-lipid). For the transfection, liposomes were loaded using a large-sized plasmid (15.5 kb), which encodes a replication-competent HIV type 1 molecular clone that carries a Gag-internal green fluorescent protein (HIV-1 JR-FL Gag-iGFP). The particle size and charge of the generated nanocarriers with 15.5 kb were compared to those of a standardized 4.7 kb plasmid formulation. Stable, small-sized lipoplexes could be generated independently of the length of the used DNA. The transfer of fluorescently labeled pDNA-HIV1-Gag-iGFP in HEK293T cells was monitored using confocal laser scanning microscopy (cLSM). After efficient plasmid delivery, virus particles were detectable as budding structures on the plasma membrane. Moreover, we observed a randomized distribution of fluorescently labeled lipids over the plasma membrane. Obviously, a significant exchange of lipids between the drug delivery system and the cellular membranes occurs, which hints toward a fusion process. The mechanism of membrane fusion for the internalization of lipid-based drug delivery systems into cells is still a frequently discussed topic.

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.

Complexation of short ds RNA/DNA oligonucleotides with Gemini micelles: a time resolved SAXS and computational study

2017 ◽  
Vol 19 (4) ◽  
pp. 3046-3055 ◽  
Author(s):  
Sara Falsini ◽  
Emanuela Di Cola ◽  
Martin In ◽  
Maria Giordani ◽  
Stefano Borocci ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Therapy ◽  
Nucleic Acid ◽  
Computational Study ◽  
Nucleic Acid Delivery ◽  
Time Resolved ◽  
Dna Oligonucleotides ◽  
P Gene

Gene therapy is based on nucleic acid delivery to pathogenic cells in order to modulate their gene expression.

scholarly journals Non-Viral Delivery of RNA Gene Therapy to the Central Nervous System

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 165
Author(s):  
Ellen S. Hauck ◽  
James G. Hecker
Keyword(s):  
Gene Therapy ◽  
Central Nervous System ◽  
Nervous System ◽  
Nucleic Acid ◽  
Gene Delivery ◽  
Dna Delivery ◽  
Clinical Applications ◽  
Cationic Lipids ◽  
Viral Dna ◽  
The Central Nervous System

Appropriate gene delivery systems are essential for successful gene therapy in clinical medicine. Lipid-mediated nucleic acid delivery is an alternative to viral vector-mediated gene delivery and has the following advantages. Lipid-mediated delivery of DNA or mRNA is usually more rapid than viral-mediated delivery, offers a larger payload, and has a nearly zero risk of incorporation. Lipid-mediated delivery of DNA or RNA is therefore preferable to viral DNA delivery in those clinical applications that do not require long-term expression for chronic conditions. Delivery of RNA may be preferable to non-viral DNA delivery in some clinical applications, since transit across the nuclear membrane is not necessary, and onset of expression with RNA is therefore even faster than with DNA, although both are faster than most viral vectors. Delivery of RNA to target organ(s) has previously been challenging due to RNA’s rapid degradation in biological systems, but cationic lipids complexed with RNA, as well as lipid nanoparticles (LNPs), have allowed for delivery and expression of the complexed RNA both in vitro and in vivo. This review will focus on the non-viral lipid-mediated delivery of RNAs, including mRNA, siRNA, shRNA, and microRNA, to the central nervous system (CNS), an organ with at least two unique challenges. The CNS contains a large number of slowly dividing or non-dividing cell types and is protected by the blood brain barrier (BBB). In non-dividing cells, RNA-lipid complexes demonstrated increased transfection efficiency relative to DNA transfection. The efficiency, timing of the onset, and duration of expression after transfection may determine which nucleic acid is best for which proposed therapy. Expression can be seen as soon as 1 h after RNA delivery, but duration of expression has been limited to 5–7 h. In contrast, transfection with a DNA lipoplex demonstrates protein expression within 5 h and lasts as long as several weeks after transfection.

scholarly journals Viral Mimicry as a Design Template for Nucleic Acid Nanocarriers

2021 ◽  
Vol 9 ◽  
Author(s):  
Ina F. de la Fuente ◽  
Shraddha S. Sawant ◽  
Mark Q. Tolentino ◽  
Patrick M. Corrigan ◽  
Jessica L. Rouge
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Molecular Mechanisms ◽  
Transfection Efficiency ◽  
Delivery Systems ◽  
Endosomal Escape ◽  
Nucleic Acid Delivery ◽  
Metastable Structure ◽  
Oligonucleotide Delivery ◽  
Genome Protection

Therapeutic nucleic acids hold immense potential in combating undruggable, gene-based diseases owing to their high programmability and relative ease of synthesis. While the delivery of this class of therapeutics has successfully entered the clinical setting, extrahepatic targeting, endosomal escape efficiency, and subcellular localization. On the other hand, viruses serve as natural carriers of nucleic acids and have acquired a plethora of structures and mechanisms that confer remarkable transfection efficiency. Thus, understanding the structure and mechanism of viruses can guide the design of synthetic nucleic acid vectors. This review revisits relevant structural and mechanistic features of viruses as design considerations for efficient nucleic acid delivery systems. This article explores how viral ligand display and a metastable structure are central to the molecular mechanisms of attachment, entry, and viral genome release. For comparison, accounted for are details on the design and intracellular fate of existing nucleic acid carriers and nanostructures that share similar and essential features to viruses. The review, thus, highlights unifying themes of viruses and nucleic acid delivery systems such as genome protection, target specificity, and controlled release. Sophisticated viral mechanisms that are yet to be exploited in oligonucleotide delivery are also identified as they could further the development of next-generation nonviral nucleic acid vectors.

scholarly journals Carriers Break Barriers in Drug Delivery: Endocytosis and Endosomal Escape of Gene Delivery Vectors

2019 ◽  
Vol 52 (7) ◽  
pp. 1750-1760 ◽  
Author(s):  
Isabelle M. S. Degors ◽  
Cuifeng Wang ◽  
Zia Ur Rehman ◽  
Inge S. Zuhorn
Keyword(s):  
Drug Delivery ◽  
Gene Delivery ◽  
Endosomal Escape ◽  
Gene Delivery Vectors

scholarly journals Efficient and Highly Specific Gene Transfer Using Mutated Lentiviral Vectors Redirected with Bispecific Antibodies

mBio ◽  
2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Christina L. Parker ◽  
Timothy M. Jacobs ◽  
Justin T. Huckaby ◽  
Dimple Harit ◽  
Samuel K. Lai
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Fluorescent Protein ◽  
Ex Vivo ◽  
Endosomal Escape ◽  
Bispecific Antibodies ◽  
Target Cells ◽  
Specific Gene ◽  
Targeted Gene Delivery

ABSTRACT Despite their exceptional potencies, the broad tropism of most commonly used lentivirus (LV) vectors limits their use for targeted gene delivery in vivo. We hypothesized that we could improve the specificity of LV targeting by coupling (i) reduction of their binding to off-target cells with (ii) redirection of the vectors with a bispecific antibody (bsAb) that binds both LV and receptors on target cells. As a proof of concept, we pseudotyped nonreplicating LV using a mutated Sindbis envelope (mSindbis) with ablated binding to native receptors, while retaining the capacity to facilitate efficient fusion and endosomal escape. We then evaluated the transduction potencies of the mSindbis LV for HER2-positive (HER2+) (SKBR3) breast and HER2-negative (HER2−) (A2780) cells when redirected with different bsAbs. mSindbis LV alone failed to induce appreciable green fluorescent protein (GFP) expression in either cell. When mixed with HER2-targeting bsAb, mSindbis LV was exceptionally potent, transducing 12% to 16% of the SKBR3 cells at a multiplicity of infection (MOI [ratio of viral genome copies to target cells]) of 3. Transduction was highly specific, resulting in ∼50-fold-greater selectivity toward SKBR3 cells versus A2780 cells. Redirecting mSindbis LV led to a 10-fold improvement in cell-specific targeting compared to redirecting wild-type Sindbis LV with the same bsAb, underscoring the importance of ablating native virus tropism in order to maximize targeting specificity. The redirection of mutated LV using bsAb represents a potent and highly versatile platform for targeted gene therapy. IMPORTANCE The goal of gene therapy is specific delivery and expression of therapeutic genes to target cells and tissues. Common lentivirus (LV) vectors are efficient gene delivery vehicles but offer little specificity. Here, we report an effective and versatile strategy to redirect LV to target cells using bispecific antibodies (bsAbs) that bind both cell receptors and LV envelope domains. Importantly, we ablated the native receptor binding of LV to minimize off-target transduction. Coupling bsAb specificity and ablated native LV tropism synergistically enhanced the selectivity of our targeted gene delivery system. The modular nature of our bsAb-based redirection enables facile targeting of the same LV to diverse tissues/cells. By abrogating the native broad tropism of LV, our bsAb-LV redirection strategy may enable lentivirus-based gene delivery in vivo, expanding the current use of LV beyond ex vivo applications.

Sign in / Sign up

Export Citation Format

Share Document