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.

scholarly journals Convection-enhanced delivery to the central nervous system

2015 ◽  
Vol 122 (3) ◽  
pp. 697-706 ◽  
Author(s):  
Russell R. Lonser ◽  
Malisa Sarntinoranont ◽  
Paul F. Morrison ◽  
Edward H. Oldfield
Keyword(s):  
Drug Delivery ◽  
Central Nervous System ◽  
Clinical Trials ◽  
Nervous System ◽  
Convective Flow ◽  
Clinical Applications ◽  
Systemic Delivery ◽  
Convection Enhanced Delivery ◽  
The Central Nervous System ◽  
Real Time Tracking

Convection-enhanced delivery (CED) is a bulk flow–driven process. Its properties permit direct, homogeneous, targeted perfusion of CNS regions with putative therapeutics while bypassing the blood-brain barrier. Development of surrogate imaging tracers that are co-infused during drug delivery now permit accurate, noninvasive real-time tracking of convective infusate flow in nervous system tissues. The potential advantages of CED in the CNS over other currently available drug delivery techniques, including systemic delivery, intrathecal and/or intraventricular distribution, and polymer implantation, have led to its application in research studies and clinical trials. The authors review the biophysical principles of convective flow and the technology, properties, and clinical applications of convective delivery in the CNS.

scholarly journals Pioneers in the cisterna magna puncture

2020 ◽  
Vol 78 (3) ◽  
pp. 176-178
Author(s):  
Thiago Ferreira Simões DE SOUZA
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Clinical Applications ◽  
Alternative Route ◽  
Cisterna Magna ◽  
Relative Safety ◽  
The Central Nervous System ◽  
Promising Source ◽  
Diagnosis Of Diseases

Abstract At the beginning of the 20th century, cerebrospinal fluid (CSF) collection and analysis emerged as a promising aid in the diagnosis of diseases of the central nervous system. It was obtained through the established procedure of lumbar puncture, described by Heinrich Quinke in 1891. The search for an alternative way to gather the CSF emerged in animal research, highlighting the cisterna magna as a promising source, with relative safety when performed by someone trained. Described initially and in detail by James Ayer in 1920, the procedure was widely adopted by neurologists and psychiatrists at the time, featuring its multiple advantages and clinical applications. After a period of great procedure use and exponential data collection, its complications and risks relegated the puncture of the cisterna magna as an alternative route that causes fear and fascination in modern Neurology.

Clinical Applications

2016 ◽  
pp. 236-252
Author(s):  
Elson L. So
Keyword(s):  
Intensive Care Unit ◽  
Central Nervous System ◽  
Nervous System ◽  
Specific Treatment ◽  
Clinical Problem ◽  
Clinical Applications ◽  
Neural Function ◽  
Central Nervous System Disorders ◽  
Progression Of Disease ◽  
The Central Nervous System

Many electrophysiological assessment and techniques of clinical neurophysiology can be used in the assessment of patients with suspected disease of the central nervous system. Each of the techniques is applied either to assist clinicians in assessing disease of the central nervous system or, less commonly, to monitor changes in neural function. These techniques can be used to monitor neural function in observing progression of disease, such as the frequency of seizures, or improvement in a patient’s condition with specific treatment. They are also used in the intensive care unit and operating room to identify progressive neural damage. The clinical neurophysiological testing technique that is most appropriate for a patient depends on the clinical problem, and, often, some combination of techniques best provides the necessary data. This chapter focuses on the application of clinical neurophysiological techniques in assessing patients with suspected central nervous system disorders.

A multicellular, neuro-mimetic model to study nanoparticle uptake in cells of the central nervous system

2014 ◽  
Vol 6 (9) ◽  
pp. 855-861 ◽  
Author(s):  
A. R. Fernandes ◽  
D. M. Chari
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Stem Cell ◽  
Gene Delivery ◽  
Neural Model ◽  
Cell Populations ◽  
Nanoparticle Uptake ◽  
System P ◽  
The Central Nervous System ◽  
In Cells

We describe a multicellular neural model to study nanoparticle uptake and gene delivery, using stem cell derived cell populations.

Nonviral Gene Delivery to the Central Nervous System Based on a Novel Integrin-Targeting Multifunctional Protein

2003 ◽  
Vol 14 (13) ◽  
pp. 1215-1223 ◽  
Author(s):  
H. Peluffo ◽  
A. Arís ◽  
L. Acarin ◽  
B. González ◽  
A. Villaverde ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Gene Delivery ◽  
Nonviral Gene Delivery ◽  
Multifunctional Protein ◽  
The Central Nervous System
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