scholarly journals Clinical Applications of Gene Therapy for Primary Immunodeficiencies

2015 ◽  
Vol 26 (4) ◽  
pp. 210-219 ◽  
Author(s):  
Maria Pia Cicalese ◽  
Alessandro Aiuti
Keyword(s):  
Gene Therapy ◽  
Clinical Applications ◽  
Primary Immunodeficiencies

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.

Gene Therapy in Primary Immunodeficiencies

2013 ◽  
Vol 02 (01) ◽  
Author(s):  
Inês Rosinha ◽  
Laura Costa ◽  
Mara Pinto ◽  
Natália Barbosa ◽  
Patrícia Rosinha
Keyword(s):  
Gene Therapy ◽  
Primary Immunodeficiencies

Gene therapy for primary immunodeficiencies: Part 2

2012 ◽  
Vol 24 (5) ◽  
pp. 585-591 ◽  
Author(s):  
Alessandro Aiuti ◽  
Rosa Bacchetta ◽  
Reinhard Seger ◽  
Anna Villa ◽  
Marina Cavazzana-Calvo
Keyword(s):  
Gene Therapy ◽  
Primary Immunodeficiencies

Gene Therapy for Primary Immunodeficiencies

2010 ◽  
Vol 30 (2) ◽  
pp. 237-248 ◽  
Author(s):  
Alain Fischer ◽  
S. Hacein-Bey-Abina ◽  
M. Cavazanna-Calvo
Keyword(s):  
Gene Therapy ◽  
Primary Immunodeficiencies

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.

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