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

scholarly journals From traditional pharmacological towards nucleic acid-based therapies for cardiovascular diseases

2020 ◽  
Vol 41 (40) ◽  
pp. 3884-3899 ◽  
Author(s):  
Ulf Landmesser ◽  
Wolfgang Poller ◽  
Sotirios Tsimikas ◽  
Patrick Most ◽  
Francesco Paneni ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Nucleic Acid ◽  
Cardiovascular Diseases ◽  
Genome Editing ◽  
Clinical Studies ◽  
Large Scale ◽  
Therapeutic Targets ◽  
Targeted Therapeutics ◽  
Gene Therapies

Abstract Nucleic acid-based therapeutics are currently developed at large scale for prevention and management of cardiovascular diseases (CVDs), since: (i) genetic studies have highlighted novel therapeutic targets suggested to be causal for CVD; (ii) there is a substantial recent progress in delivery, efficacy, and safety of nucleic acid-based therapies; (iii) they enable effective modulation of therapeutic targets that cannot be sufficiently or optimally addressed using traditional small molecule drugs or antibodies. Nucleic acid-based therapeutics include (i) RNA-targeted therapeutics for gene silencing; (ii) microRNA-modulating and epigenetic therapies; (iii) gene therapies; and (iv) genome-editing approaches (e.g. CRISPR-Cas-based): (i) RNA-targeted therapeutics: several large-scale clinical development programmes, using antisense oligonucleotides (ASO) or short interfering RNA (siRNA) therapeutics for prevention and management of CVD have been initiated. These include ASO and/or siRNA molecules to lower apolipoprotein (a) [apo(a)], proprotein convertase subtilisin/kexin type 9 (PCSK9), apoCIII, ANGPTL3, or transthyretin (TTR) for prevention and treatment of patients with atherosclerotic CVD or TTR amyloidosis. (ii) MicroRNA-modulating and epigenetic therapies: novel potential therapeutic targets are continually arising from human non-coding genome and epigenetic research. First microRNA-based therapeutics or therapies targeting epigenetic regulatory pathways are in clinical studies. (iii) Gene therapies: EMA/FDA have approved gene therapies for non-cardiac monogenic diseases and LDL receptor gene therapy is currently being examined in patients with homozygous hypercholesterolaemia. In experimental studies, gene therapy has significantly improved cardiac function in heart failure animal models. (iv) Genome editing approaches: these technologies, such as using CRISPR-Cas, have proven powerful in stem cells, however, important challenges are remaining, e.g. low rates of homology-directed repair in somatic cells such as cardiomyocytes. In summary, RNA-targeted therapies (e.g. apo(a)-ASO and PCSK9-siRNA) are now in large-scale clinical outcome trials and will most likely become a novel effective and safe therapeutic option for CVD in the near future. MicroRNA-modulating, epigenetic, and gene therapies are tested in early clinical studies for CVD. CRISPR-Cas-mediated genome editing is highly effective in stem cells, but major challenges are remaining in somatic cells, however, this field is rapidly advancing.

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

Gene Therapy in Cardiovascular Diseases

2002 ◽  
Vol 2 (4) ◽  
pp. 427-435 ◽  
Author(s):  
Kamala Tamirisa ◽  
Debabrata Mukherjee
Keyword(s):  
Gene Therapy ◽  
Cardiovascular Diseases

Gene therapy in cardiovascular diseases: A review of recent updates

2018 ◽  
Vol 119 (12) ◽  
pp. 9645-9654 ◽  
Author(s):  
Armita M. Gorabi ◽  
Saeideh Hajighasemi ◽  
Hossein A. Tafti ◽  
Masoud Soleimani ◽  
Yunes Panahi ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Cardiovascular Diseases

Development of simplified and rapid nucleic acid release protocol for PCR based detection of Potato viruses

2018 ◽  
Vol 46 (2) ◽  
pp. 255-262 ◽  
Author(s):  
Baswaraj Raigond ◽  
Ambika Verma ◽  
Tarvinder Kochhar ◽  
Shivani Roach ◽  
Sanjeev Sharma ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Potato Viruses ◽  
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.

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.

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