Sonodelivery in Skeletal Muscle: Current Approaches and Future Potential

There are currently multiple approaches to facilitate gene therapy via intramuscular gene delivery, such as electroporation, viral delivery, or direct DNA injection with or without polymeric carriers. Each of these methods has benefits, but each method also has shortcomings preventing it from being established as the ideal technique. A promising method, ultrasound-mediated gene delivery (or sonodelivery) is inexpensive, widely available, reusable, minimally invasive, and safe. Hurdles to utilizing sonodelivery include choosing from a large variety of conditions, which are often dependent on the equipment and/or research group, and moderate transfection efficiencies when compared to some other gene delivery methods. In this review, we provide a comprehensive look at the breadth of sonodelivery techniques for intramuscular gene delivery and suggest future directions for this continuously evolving field.

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Crotamine as a vehicle for non-viral gene delivery for Pompe disease

10.1101/2021.03.23.436632 ◽

2021 ◽

Author(s):

Frank Martiniuk ◽

Adra Mack ◽

Justin Martiniuk ◽

Richard Karpel ◽

Peter Meinke ◽

...

Keyword(s):

Skeletal Muscle ◽

Gene Therapy ◽

Gene Delivery ◽

Pompe Disease ◽

Cell Penetrating Peptides ◽

Biologically Active ◽

Viral Gene ◽

Time Activity ◽

Acid Maltase ◽

Alglucosidase Alfa

Genetic deficiency of lysosomal acid alpha glucosidase or acid maltase (GAA) results in Pompe disease (PD), encompassing at least five clinical subtypes of varying severity. The current approved enzyme replacement therapy (ERT) for PD is via IV infusion every 2 weeks of a recombinant human GAA (rhGAA) secreted by Chinese hamster ovary (CHO) cells (alglucosidase alfa/Myozyme, Sanofi/Genzyme). Although alglucosidase alfa has proven to be efficient in rescuing cardiac abnormalities and extending the life span of the infantile form, the response in skeletal muscle is variable. ERT usually begins when the patients are symptomatic and secondary problems are already present which are compounded by low alglucosidase alfa uptake, transient nature (every 2 weeks with a rapid return to defect levels), variable glycogen reduction, autophagic accumulation, immune response and high cost. A consensus at a recent US Acid Maltase Deficiency (AMD) conference suggested that a multi-pronged approach including gene therapy, diet, exercise, etc. must be evaluated for a successful treatment of PD. Compared to replication defective viruses, non-viral gene transfer offers fewer safety concerns and, if recent studies are validated, has a wider range of cells. In order for gene therapy (GT) to succeed, the gene of interest must be delivered into the affected cell and expressed to overcome the inherited deficiency. Cell penetrating peptides (CPPs) enter eukaryotic cells through an energy-independent mechanism and efficiently carry biologically active and therapeutic molecules into cells and localize in the cytoplasm or nucleus. CPPs are usually covalently linked to the cargo, including peptides and DNA. Crotamine (Cro) from the South American rattlesnake-Crotalus durrissus terrificus venom, can bind electrostatically to plasmid DNA to deliver into cells, including muscle. We have assembled a bacterial expression vector for Cro and purified the recombinant Cro (rCro). Transient transfection in AMD fibroblasts and ex vivo in whole blood from an adult Pompe patient with rCro complexed with the pcDNA3 x hGAA cDNA demonstrated increased GAA activity. In GAA knockout (KO) mice receiving a single injection of rCro complexed to pcDNA3 x hGAA cDNA intraperitoneally (IP), we found increased GAA activity in tissues after 48 hr. After 8 treatments-IP over 55 days, we found increased vertical hang-time activity, reduced glycogen deposition, increased GAA activity/hGAA plasmid in tissues and minimal immune-reaction to rCro. A subsequent study of 5 administrations every 2 to 3 weeks showed reverse of the clinical phenotypes by running wheel activity, Rotarod, grip-strength meter, open field mobility and T-maze. Tissue culture experiments in PD fibroblast, lymphoid and skeletal muscle cell lines showed increased GAA activity after rCro transient gene delivery.

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Role of αv Integrins in Adenovirus Cell Entry and Gene Delivery

Microbiology and Molecular Biology Reviews ◽

10.1128/mmbr.63.3.725-734.1999 ◽

1999 ◽

Vol 63 (3) ◽

pp. 725-734 ◽

Cited By ~ 177

Author(s):

Glen R. Nemerow ◽

Phoebe L. Stewart

Keyword(s):

Gene Therapy ◽

Gene Delivery ◽

Human Gene ◽

Distinct Advantage ◽

Delivery Methods ◽

Significant Information ◽

Human Gene Therapy ◽

Current State ◽

Almost All ◽

And Function

SUMMARY Adenoviruses (Ad) are a significant cause of acute infections in humans; however, replication-defective forms of this virus are currently under investigation for human gene therapy. Approximately 20 to 25% of all the gene therapy trials (phases I to III) conducted over the past 10 years involve the use of Ad gene delivery for treatment inherited or acquired diseases. At present, the most promising applications involve the use of Ad vectors to irradicate certain nonmetastatic tumors and to promote angiogenesis in order to alleviate cardiovascular disease. While specific problems of using Ad vectors remain to be overcome (as is true for almost all viral and nonviral delivery methods), a distinct advantage of Ad is the extensive knowledge of its macromolecular structure, genome organization, sequence, and mode of replication. Moreover, significant information has also been acquired on the interaction of Ad particles with distinct host cell receptors, events which strongly affect virus tropism. This review provides an overview of the structure and function of Ad attachment (coxsackievirus and Ad receptor [CAR]) and internalization (αv integrins) receptors and discusses their precise role in virus infection and gene delivery. Recent structure studies of integrin-Ad complexes by cryoelectron microscopy are also highlighted. Finally, unanswered questions arising from the current state of knowledge of Ad-receptor interactions are presented in the context of improving Ad vectors for future human gene therapy applications.

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Cardiac disease: Current approaches to gene therapy

Bulletin of Medical and Clinical Research ◽

10.34256/br2017 ◽

2020 ◽

pp. 62-75

Author(s):

Reyad ul-ferdous ◽

◽

Shofiul Azam ◽

◽

...

Keyword(s):

Gene Therapy ◽

Clinical Trials ◽

Gene Delivery ◽

Cardiac Disease ◽

Target Genes ◽

Viral Vector ◽

Delivery Methods ◽

Gene Therapies ◽

Inherited Cardiomyopathies

Background: Last decade over the world, the cardiac disease becomes a leading cause of death. Gene-based therapies become a promising treatment for patients affected by cardiovascular diseases, such as myocardial infarction (MI), arteriosclerosis, heart failure and so on, but also underline the require for reproducible results in preclinical and clinical studies for efficacy and safety. Aim: This book chapter describes the current research prospect of gene therapy for cardiac disease. We focus on the various models to deliver genes using viral, non-viral vector, delivery methods, targets gene, recent clinical trials, inherited cardiomyopathies target genes and Present advances of CRISPR/Cas 9 for cardiovascular gene therapy. We recapitulate some challenges that require being overcome, future directions of gene therapies for cardiac disease. Materials and Methods: All required information regards Lef-7 was generated by exploring the internet search engine like as (PubMed, Wiley, ScienceDirect, CNKI, ACS, Google Scholar, Web of Science, SciFinder, and Baidu Scholar) and libraries. Results: In this book chapter, we focus on the present prospect of gene targets, gene delivery methods, and efficient vector to deliver gene, targets gene, recent clinical trials, inherited cardiomyopathies target genes and present advances of CRISPR/Cas 9 technology for the treatment of cardiac disease using gene therapy. Recent clinical trials require modifying vectors and gene delivery approaches to achieve effective results for cardiac gene therapy. Conclusion: In this book chapter, we integrate a historical perspective with recent advances that will likely affect clinical development in this research area.

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Development of in vivo gene delivery methods in mice using tissue suction devices for abdominal endoscopic gene therapy

2012 International Symposium on Micro-NanoMechatronics and Human Science (MHS) ◽

10.1109/mhs.2012.6492389 ◽

2012 ◽

Author(s):

Kazunori Shimizu ◽

Shigeru Kawakami ◽

Kouji Hayashi ◽

Shingo Katano ◽

Guangyuan Zhang ◽

...

Keyword(s):

Gene Therapy ◽

Gene Delivery ◽

Delivery Methods ◽

In Vivo Gene Delivery

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Gene delivery methods in cardiac gene therapy

The Journal of Gene Medicine ◽

10.1002/jgm.1609 ◽

2011 ◽

Vol 13 (10) ◽

pp. 566-572 ◽

Cited By ~ 30

Author(s):

Kiyotake Ishikawa ◽

Lisa Tilemann ◽

Kenneth Fish ◽

Roger J. Hajjar

Keyword(s):

Gene Therapy ◽

Gene Delivery ◽

Delivery Methods ◽

Cardiac Gene

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Gene Therapy for Heart Disease: Modified mRNA Perspectives

10.5772/intechopen.97184 ◽

2021 ◽

Author(s):

Lior Zangi ◽

Ravinder K. Kaundal ◽

Keerat Kaur

Keyword(s):

Gene Therapy ◽

Heart Disease ◽

Molecular Mechanisms ◽

Cardiac Repair ◽

The Body ◽

Therapeutic Approaches ◽

Delivery Methods ◽

Future Directions ◽

Promising Alternative ◽

Compositional Changes

Ischemic heart disease (IHD) presents a gigantic clinical challenge that demands effective therapeutic approaches. With increasing knowledge of the basic molecular mechanisms guiding the progress of this disease, it is now possible to target the key pathological players through gene therapy. Modified mRNA-based gene delivery presents a promising alternative to traditional gene therapy, because modRNA approaches have high potency, non-immunogenicity, greater efficiency and controlled nucleic acid transfer to the body. However, until recently the therapeutic applications of mRNA have been limited, as naturally occurring mRNA is rapidly degraded and cleared from the circulation. In this chapter, we outline the compositional changes made to mRNA to enhance its translational capacity and discuss the available carrier molecules currently being employed to deliver modRNA to the heart. We provide a detailed overview of modRNA applicability for cardiac repair and regeneration and consider future directions for novel delivery methods that can facilitate its cardiac therapeutic use.

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Targeting the heart with gene therapy-optimized gene delivery methods

Cardiovascular Research ◽

10.1016/j.cardiores.2006.09.021 ◽

2007 ◽

Vol 73 (3) ◽

pp. 453-462 ◽

Cited By ~ 79

Author(s):

O MULLER ◽

H KATUS ◽

R BEKEREDJIAN

Keyword(s):

Gene Therapy ◽

Gene Delivery ◽

Delivery Methods

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Practical gene delivery system suitable for clinical gene therapy

Nature Middle East ◽

10.1038/nmiddleeast.2010.238 ◽

2010 ◽

Author(s):

Abdulhakim Mahmoud

Keyword(s):

Gene Therapy ◽

Gene Delivery ◽

Delivery System ◽

Gene Delivery System ◽

Clinical Gene Therapy

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Exosome as a Natural Gene Delivery Vector for Cancer Treatment

Current Cancer Drug Targets ◽

10.2174/1568009620666200924154149 ◽

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.

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