“Dosimetric optimization of interstitial gene therapy delivery systems”

2009 ◽  
Author(s):  
Kenneth H. Wong
Keyword(s):  
Gene Therapy ◽  
Delivery Systems ◽  
Therapy Delivery

scholarly journals Gene Therapy Delivery Systems for Enhancing Viral and Nonviral Vectors for Cardiac Diseases: Current Concepts and Future Applications

2013 ◽  
Vol 24 (11) ◽  
pp. 914-927 ◽  
Author(s):  
Michael G. Katz ◽  
Anthony S. Fargnoli ◽  
Richard D. Williams ◽  
Charles R. Bridges
Keyword(s):  
Gene Therapy ◽  
Delivery Systems ◽  
Cardiac Diseases ◽  
Nonviral Vectors ◽  
Therapy Delivery

A Review of Gene Therapy Delivery Systems for Intervertebral Disc Degeneration

2020 ◽  
Vol 21 (3) ◽  
pp. 194-205 ◽  
Author(s):  
Songfeng Chen ◽  
Ming Luo ◽  
Hongwei Kou ◽  
Guowei Shang ◽  
Yanhui Ji ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Intervertebral Disc ◽  
Viral Vectors ◽  
English Language ◽  
New Technologies ◽  
Viral Vector ◽  
Delivery Systems ◽  
Health Concern ◽  
Ivd Degeneration ◽  
Therapy Delivery

Background: : Intervertebral Disc (IVD) degeneration is a major public health concern, and gene therapy seems a promising approach to delay or even reverse IVD degeneration. However, the delivery system used to transfer exogenous genes into intervertebral disc cells remains a challenge. Methods:: The MEDLINE, Web of Science, and Scopus databases were searched for English-language articles related to gene therapy for IVD degeneration articles from 1999 to May 2019. The keywords included “gene therapy” AND “intervertebral disc”. The history of the development of different delivery systems was analysed, and the latest developments in viral and non-viral vectors for IVD degeneration treatment were reviewed. Results: : Gene therapy delivery systems for IVD degeneration are divided into two broad categories: viral and non-viral vectors. The most commonly used viral vectors are adenovirus, adeno-associated virus (AAV), and lentivirus. Enthusiasm for the use of adenovirus vectors has gradually declined and has been replaced by a preference for lentivirus and AAV vectors. New technologies, such as RNAi and CRISPR, have further enhanced the advantage of viral vectors. Liposomes are the classic non-viral vector, and their successors, polyplex micelles and exosomes, have more potential for use in gene therapy for IVD degeneration. Conclusion:: Lentivirus and AAV are the conventional viral vectors used in gene therapy for IVD degeneration, and the new technologies RNAi and CRISPR have further enhanced their advantages. Nonviral vectors, such as polyplex micelles and exosomes, are promising gene therapy vectors for IVD degeneration.

scholarly journals Intracellular Routing and Recognition of Lipid-Based mRNA Nanoparticles

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 945
Author(s):  
Christophe Delehedde ◽  
Luc Even ◽  
Patrick Midoux ◽  
Chantal Pichon ◽  
Federico Perche
Keyword(s):  
Gene Therapy ◽  
Immune Responses ◽  
Transient Expression ◽  
Messenger Rna ◽  
Lipid Nanoparticles ◽  
Delivery Systems ◽  
Clinical Applications ◽  
Cellular Proteins ◽  
Mrna Sequence ◽  
Cytoplasmic Expression

Messenger RNA (mRNA) is being extensively used in gene therapy and vaccination due to its safety over DNA, in the following ways: its lack of integration risk, cytoplasmic expression, and transient expression compatible with fine regulations. However, clinical applications of mRNA are limited by its fast degradation by nucleases, and the activation of detrimental immune responses. Advances in mRNA applications, with the recent approval of COVID-19 vaccines, were fueled by optimization of the mRNA sequence and the development of mRNA delivery systems. Although delivery systems and mRNA sequence optimization have been abundantly reviewed, understanding of the intracellular processing of mRNA is mandatory to improve its applications. We will focus on lipid nanoparticles (LNPs) as they are the most advanced nanocarriers for the delivery of mRNA. Here, we will review how mRNA therapeutic potency can be affected by its interactions with cellular proteins and intracellular distribution.

scholarly journals Growth Factor Therapy for Parkinson’s Disease: Alternative Delivery Systems

2021 ◽  
pp. 1-7
Author(s):  
Sarah Jarrin ◽  
Abrar Hakami ◽  
Ben Newland ◽  
Eilís Dowd
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Growth Factors ◽  
Growth Factor ◽  
Ex Vivo ◽  
Brain Regions ◽  
Delivery Systems ◽  
Alternative Delivery

Despite decades of research and billions in global investment, there remains no preventative or curative treatment for any neurodegenerative condition, including Parkinson’s disease (PD). Arguably, the most promising approach for neuroprotection and neurorestoration in PD is using growth factors which can promote the growth and survival of degenerating neurons. However, although neurotrophin therapy may seem like the ideal approach for neurodegenerative disease, the use of growth factors as drugs presents major challenges because of their protein structure which creates serious hurdles related to accessing the brain and specific targeting of affected brain regions. To address these challenges, several different delivery systems have been developed, and two major approaches—direct infusion of the growth factor protein into the target brain region and in vivo gene therapy—have progressed to clinical trials in patients with PD. In addition to these clinically evaluated approaches, a range of other delivery methods are in various degrees of development, each with their own unique potential. This review will give a short overview of some of these alternative delivery systems, with a focus on ex vivo gene therapy and biomaterial-aided protein and gene delivery, and will provide some perspectives on their potential for clinical development and translation.

scholarly journals Next Step in Gene Delivery: Modern Approaches and Further Perspectives of AAV Tropism Modification

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 750
Author(s):  
Maxim A. Korneyenkov ◽  
Andrey A. Zamyatnin
Keyword(s):  
Gene Therapy ◽  
Genome Organization ◽  
Rational Design ◽  
Structural Data ◽  
Rational Approach ◽  
Tissue Tropism ◽  
Adeno Associated Virus ◽  
Chemical Conjugation ◽  
The Usa ◽  
Therapy Delivery

Today, adeno-associated virus (AAV) is an extremely popular choice for gene therapy delivery. The safety profile and simplicity of the genome organization are the decisive advantages which allow us to claim that AAV is currently among the most promising vectors. Several drugs based on AAV have been approved in the USA and Europe, but AAV serotypes’ unspecific tissue tropism is still a serious limitation. In recent decades, several techniques have been developed to overcome this barrier, such as the rational design, directed evolution and chemical conjugation of targeting molecules with a capsid. Today, all of the abovementioned approaches confer the possibility to produce AAV capsids with tailored tropism, but recent data indicate that a better understanding of AAV biology and the growth of structural data may theoretically constitute a rational approach to most effectively produce highly selective and targeted AAV capsids. However, while we are still far from this goal, other approaches are still in play, despite their drawbacks and limitations.

scholarly journals Delivery systems of CRISPR/Cas9-based cancer gene therapy

2018 ◽  
Vol 12 (1) ◽  
Author(s):  
Alessio Biagioni ◽  
Anna Laurenzana ◽  
Francesca Margheri ◽  
Anastasia Chillà ◽  
Gabriella Fibbi ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Cancer Gene Therapy ◽  
Delivery Systems ◽  
Cancer Gene

scholarly journals Сationic liposomes as delivery systems for nucleic acids

2020 ◽  
Vol 15 (1) ◽  
pp. 7-27
Author(s):  
A. A. Mikheev ◽  
E. V. Shmendel ◽  
E. S. Zhestovskaya ◽  
G. V. Nazarov ◽  
M. A. Maslov
Keyword(s):  
Gene Therapy ◽  
Nucleic Acids ◽  
Serum Proteins ◽  
Transfection Efficiency ◽  
Biological Fluids ◽  
Genetic Material ◽  
Cationic Liposomes ◽  
Delivery Systems ◽  
Cationic Lipids

Objectives. Gene therapy is based on the introduction of genetic material into cells, tissues, or organs for the treatment of hereditary or acquired diseases. A key factor in the success of gene therapy is the development of delivery systems that can efficiently transfer genetic material to the place of their therapeutic action without causing any associated side effects. Over the past 10 years, significant effort has been directed toward creating more efficient and biocompatible vectors capable of transferring nucleic acids (NAs) into cells without inducing an immune response. Cationic liposomes are among the most versatile tools for delivering NAs into cells; however, the use of liposomes for gene therapy is limited by their low specificity. This is due to the presence of various biological barriers to the complex of liposomes with NA, including instability in biological fluids, interaction with serum proteins, plasma and nuclear membranes, and endosomal degradation. This review summarizes the results of research in recent years on the development of cationic liposomes that are effective in vitro and in vivo. Particular attention is paid to the individual structural elements of cationic liposomes that determine the transfection efficiency and cytotoxicity. The purpose of this review was to provide a theoretical justification of the most promising choice of cationic liposomes for the delivery of NAs into eukaryotic cells and study the effect of the composition of cationic lipids (CLs) on the transfection efficiency in vitro.Results. As a result of the analysis of the related literature, it can be argued that one of the most promising delivery systems of NAs is CL based on cholesterol and spermine with the addition of a helper lipid DOPE. In addition, it was found that varying the composition of cationic liposomes, the ratio of CL to NA, or the size and zeta potential of liposomes has a significant effect on the transfection efficiency.Conclusions. Further studies in this direction should include optimization of the conditions for obtaining cationic liposomes, taking into account the physicochemical properties and established laws. It is necessary to identify mechanisms that increase the efficiency of NA delivery in vitro by searching for optimal structures of cationic liposomes, determining the ratio of lipoplex components, and studying the delivery efficiency and properties of multicomponent liposomes.

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