scholarly journals Non-Viral Nucleic Acid Delivery Strategies to the Central Nervous System

2016 ◽  
Vol 9 ◽  
Author(s):  
James-Kevin Y. Tan ◽  
Drew L. Sellers ◽  
Binhan Pham ◽  
Suzie H. Pun ◽  
Philip J. Horner
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nucleic Acid ◽  
Nucleic Acid Delivery ◽  
Viral Nucleic Acid ◽  
The Central Nervous System ◽  
Delivery Strategies

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.

Expression and functional analysis of nucleic acid sensors in cells of the central nervous system

2014 ◽  
Vol 275 (1-2) ◽  
pp. 83
Author(s):  
Donal Cox ◽  
Glyn Williams ◽  
Neil Kearney ◽  
Andrew Bowie ◽  
Marina Lynch ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Functional Analysis ◽  
Nervous System ◽  
Nucleic Acid ◽  
The Central Nervous System ◽  
In Cells ◽  
Acid Sensors

scholarly journals Detection of SARS-CoV-2 nucleic acid in CSF by ultrahigh depth sequencing in a patient with COVID-19 and neurological dysfunction: a case report

2020 ◽  
Author(s):  
Pan Xiang ◽  
Xinmin Xu ◽  
Xin Lu ◽  
Lili Gao ◽  
Huizhu Wang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Nucleic Acid ◽  
Neural Progenitor Cells ◽  
Central Nervous System Infection ◽  
Neurological Dysfunction ◽  
Human Neural Progenitor Cells ◽  
The Central Nervous System

Abstract Background: SARS-Coronavirus-2 (SARS-CoV-2), the pathogen of coronavirus disease 2019 (COVID-19), not only infects the respiratory tract, but also other organs. About a third of the inpatients of COVID-19 have neurological symptoms and in vitro experiments revealed that SARS-CoV-2 could infect human neural progenitor cells and brain organoids. However, the traditional test often reports negative owing to the low number of virus in the cerebrospinal fluid. To date, timely diagnosis of central nervous system infection of SARS-CoV-2 remains a challenge.Case presentation: On day 14 of COVID-19, seizures, maxillofacial convulsions, intractable hiccups and significant increase in intracranial pressure developed in a 56-year-old man. The RT-PCR of SARS-CoV-2 was negative. SARS-CoV-2 nucleic acid were detected in cerebrospinal fluid (CSF) by ultrahigh depth sequencing. The patient was successfully treated after 14 days of mechanical ventilation and treatment of pneumonia and neurological dysfunction.Conclusions: This case suggests SARS-CoV-2 can invade the central nervous system and relevant examinations with CSF including ultrahigh depth sequencing of SARS-CoV-2 are needed among COVID-19 patients with neurological dysfunction.

scholarly journals Crossing the Blood-Brain Barrier: A Review on Drug Delivery Strategies for Treatment of the Central Nervous System Diseases

2019 ◽  
Vol 16 (8) ◽  
pp. 698-711 ◽  
Author(s):  
Nur Izzati Mansor ◽  
Norshariza Nordin ◽  
Farahidah Mohamed ◽  
King Hwa Ling ◽  
Rozita Rosli ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Diseases ◽  
Advantages And Disadvantages ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Delivery Strategies

: Many drugs have been designed to treat diseases of the central nervous system (CNS), especially neurodegenerative diseases. However, the presence of tight junctions at the blood-brain barrier has often compromised the efficiency of drug delivery to target sites in the brain. The principles of drug delivery systems across the blood-brain barrier are dependent on substrate-specific (i.e. protein transport and transcytosis) and non-specific (i.e. transcellular and paracellular) transport pathways, which are crucial factors in attempts to design efficient drug delivery strategies. This review describes how the blood-brain barrier presents the main challenge in delivering drugs to treat brain diseases and discusses the advantages and disadvantages of ongoing neurotherapeutic delivery strategies in overcoming this limitation. In addition, we discuss the application of colloidal carrier systems, particularly nanoparticles, as potential tools for therapy for the CNS diseases.

The biochemistry of copper deficiency - II. Synthetic processes

1956 ◽  
Vol 145 (919) ◽  
pp. 195-205 ◽  
Keyword(s):  
Fatty Acids ◽  
Central Nervous System ◽  
Nervous System ◽  
Nucleic Acid ◽  
Copper Deficiency ◽  
Long Chain Fatty Acids ◽  
Phospholipid Synthesis ◽  
The Central Nervous System ◽  
Long Chain ◽  
Chain Fatty Acids

The biochemistry of copper deficiency is studied in order to gain some understanding of the metabolic disturbances which lead to demyelination of the central nervous system in disease. In the preceding paper we reported our investigation of the enzyme systems, blood chemistry and amino-acid excretion in copper-deficient rats, and in this paper extend the study to investigate the syntheses of phospholipid, long-chain fatty acids, ribose nucleic acid, protein and protohaem. Phospholipid synthesis is found to be depressed considerably in copper deficiency. This is due to a failure in the process of condensation of acyl CoA with α-glycerophosphate to form phosphatidic acids. The reasons are discussed. The syntheses of long-chain fatty acids and ribose nucleic acid are normal, whilst the synthesis of protein is inconstantly affected by copper deficiency. Protohaem synthesis is depressed by a degree which exactly parallels the anaemia. The conclusion is drawn that the anaemia is due to a decrease in haematopoiesis rather than an increased destruction of red cells. The possible interrelationships of the disturbances of phospholipid synthesis and cytochrome oxidase activity and the relevance of each to demyelination of the central nervous system are discussed.

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