Viral Vectors: A Wide Range of Choices and High Levels of Service

2007 ◽  
pp. 177-202 ◽  
Author(s):  
P. Osten ◽  
V. Grinevich ◽  
A. Cetin
Keyword(s):  
Viral Vectors ◽  
Wide Range ◽  
Levels Of Service

scholarly journals Optimising T cell (re)boosting strategies for adenoviral and modified vaccinia Ankara vaccine regimens in humans

npj Vaccines ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Stefania Capone ◽  
Anthony Brown ◽  
Felicity Hartnell ◽  
Mariarosaria Del Sorbo ◽  
Cinzia Traboni ◽  
...  
Keyword(s):  
T Cells ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
T Cell ◽  
Viral Vectors ◽  
Standard Dose ◽  
T Cell Responses ◽  
Effector Memory ◽  
Cell Responses ◽  
Wide Range

Abstract Simian adenoviral and modified vaccinia Ankara (MVA) viral vectors used in heterologous prime-boost strategies are potent inducers of T cells against encoded antigens and are in advanced testing as vaccine carriers for a wide range of infectious agents and cancers. It is unclear if these responses can be further enhanced or sustained with reboosting strategies. Furthermore, despite the challenges involved in MVA manufacture dose de-escalation has not been performed in humans. In this study, healthy volunteers received chimpanzee-derived adenovirus-3 and MVA vaccines encoding the non-structural region of hepatitis C virus (ChAd3-NSmut/MVA-NSmut) 8 weeks apart. Volunteers were then reboosted with a second round of ChAd3-NSmut/MVA-NSmut or MVA-NSmut vaccines 8 weeks or 1-year later. We also determined the capacity of reduced doses of MVA-NSmut to boost ChAd3-NSmut primed T cells. Reboosting was safe, with no enhanced reactogenicity. Reboosting after an 8-week interval led to minimal re-expansion of transgene-specific T cells. However, after a longer interval, T cell responses expanded efficiently and memory responses were enhanced. The 8-week interval regimen induced a higher percentage of terminally differentiated and effector memory T cells. Reboosting with MVA-NSmut alone was as effective as with ChAd3-NSmut/MVA-NSmut. A ten-fold lower dose of MVA (2 × 107pfu) induced high-magnitude, sustained, broad, and functional Hepatitis C virus (HCV)-specific T cell responses, equivalent to standard doses (2 × 108 pfu). Overall, we show that following Ad/MVA prime-boost vaccination reboosting is most effective after a prolonged interval and is productive with MVA alone. Importantly, we also show that a ten-fold lower dose of MVA is as potent in humans as the standard dose.

Gene therapy for neurodegenerative and ocular diseases using lentiviral vectors

2005 ◽  
Vol 110 (1) ◽  
pp. 37-46 ◽  
Author(s):  
G. Scott Ralph ◽  
Katie Binley ◽  
Liang-Fong Wong ◽  
Mimoun Azzouz ◽  
Nicholas D. Mazarakis
Keyword(s):  
Gene Therapy ◽  
Nervous System ◽  
Viral Vectors ◽  
Viral Vector ◽  
Lentiviral Vectors ◽  
Great Promise ◽  
Ocular Diseases ◽  
Vector Systems ◽  
Gene Therapy Application ◽  
Wide Range

Gene therapy holds great promise for the treatment of a wide range of inherited and acquired disorders. The development of viral vector systems to mediate safe and long-lasting expression of therapeutic transgenes in specific target cell populations is continually advancing. Gene therapy for the nervous system is particularly challenging due to the post-mitotic nature of neuronal cells and the restricted accessibility of the brain itself. Viral vectors based on lentiviruses provide particularly attractive vehicles for delivery of therapeutic genes to treat neurological and ocular diseases, since they efficiently transduce non-dividing cells and mediate sustained transgene expression. Furthermore, novel routes of vector delivery to the nervous system have recently been elucidated and these have increased further the scope of lentiviruses for gene therapy application. Several studies have demonstrated convincing therapeutic efficacy of lentiviral-based gene therapies in animal models of severe neurological disorders and the push for progressing such vectors to the clinic is ongoing. This review describes the key features of lentiviral vectors that make them such useful tools for gene therapy to the nervous system and outlines the major breakthroughs in the potential use of such vectors for treating neurodegenerative and ocular diseases.

scholarly journals Advances in Genome Editing With CRISPR Systems and Transformation Technologies for Plant DNA Manipulation

2021 ◽  
Vol 11 ◽  
Author(s):  
Satya Swathi Nadakuduti ◽  
Felix Enciso-Rodríguez
Keyword(s):  
Genome Editing ◽  
Viral Vectors ◽  
Gene Editing ◽  
De Novo ◽  
Alternative Methods ◽  
Zinc Finger Nucleases ◽  
Target Range ◽  
Homing Endonucleases ◽  
Plant Gene ◽  
Wide Range

The year 2020 marks a decade since the first gene-edited plants were generated using homing endonucleases and zinc finger nucleases. The advent of CRISPR/Cas9 for gene-editing in 2012 was a major science breakthrough that revolutionized both basic and applied research in various organisms including plants and consequently honored with “The Nobel Prize in Chemistry, 2020.” CRISPR technology is a rapidly evolving field and multiple CRISPR-Cas derived reagents collectively offer a wide range of applications for gene-editing and beyond. While most of these technological advances are successfully adopted in plants to advance functional genomics research and development of innovative crops, others await optimization. One of the biggest bottlenecks in plant gene-editing has been the delivery of gene-editing reagents, since genetic transformation methods are only established in a limited number of species. Recently, alternative methods of delivering CRISPR reagents to plants are being explored. This review mainly focuses on the most recent advances in plant gene-editing including (1) the current Cas effectors and Cas variants with a wide target range, reduced size and increased specificity along with tissue specific genome editing tool kit (2) cytosine, adenine, and glycosylase base editors that can precisely install all possible transition and transversion mutations in target sites (3) prime editing that can directly copy the desired edit into target DNA by search and replace method and (4) CRISPR delivery mechanisms for plant gene-editing that bypass tissue culture and regeneration procedures including de novo meristem induction, delivery using viral vectors and prospects of nanotechnology-based approaches.

scholarly journals The Use of Viral Vectors in Gene Transfer Therapy

2016 ◽  
Vol 8 (03) ◽  
Author(s):  
A. Dziaková ◽  
A. Valenčáková ◽  
E. Hatalová ◽  
J. Kalinová
Keyword(s):  
Gene Therapy ◽  
Plasmid Dna ◽  
Clinical Studies ◽  
Viral Vectors ◽  
Disease Gene ◽  
Major Gene ◽  
Genetic Material ◽  
The Body ◽  
Disease Genes ◽  
Wide Range

Gene therapy is strategy based on using genes as pharmaceuticals. Gene therapy is a treatment that involves altering the genes inside body's cells to stop disease. Genes contain DNA- the code controlling body form and function. Genes that do not work properly can cause disease. Gene therapy replaces a faulty gene or adds a new gene in an attempt to cure disease or improve the ability of the body to fight disease. Gene therapy holds promise for treating a wide range of diseases, including cancer, cystic fibrosis, heart disease, diabetes, hemophilia and AIDS. Various types of genetic material are used in gene therapy; double-stranded DNA (dsDNA), single-stranded DNA (ssDNA), plasmid DNA and antisense oligodeoxynucleotides (ASON). The success of gene therapy depends on assuring the entrance of the therapeutic gene to targeted cells without any form of biodegradation. Commonly used vectors in gene therapy are: adenoviruses (400 clinical studies; 23.8%), retroviruses (344 clinical studies; 20.5%), unenveloped/plasmid DNA (304 clinical studies, 17.7%), adenoassociated viruses (75 clinical studies; 4.5%) and others. In this paper, we have reviewed the major gene delivery vectors and recent improvements made in their design meant to overcome the issues that commonly arise with the use of gene therapy vectors.

scholarly journals An extended toolkit for production and use of RVdG-CVS-N2c rabies viral vectors uncovers hidden hippocampal connections

2021 ◽  
Author(s):  
Anton Sumser ◽  
Maximilian Joesch ◽  
Peter Jonas ◽  
Yoav Ben-Simon
Keyword(s):  
Viral Vectors ◽  
Molecular Tools ◽  
Cell Type ◽  
Large Collection ◽  
Neuronal Connectivity ◽  
Retrograde Labeling ◽  
Neuronal Populations ◽  
Wide Range ◽  
Cell Type Specific ◽  
Cortical Microcircuit

From the large collection of molecular tools used to investigate neuronal connectivity, envA-pseudotyped rabies viral vectors (RVdGenvA) uniquely enable cell-type specific, trans-synaptic retrograde labeling. However, widespread use of the powerful and flexible method is to date hindered by low-yield and cumbersome production pipelines. Here, we report the development of new cell lines, which significantly reduce production time while increasing viral titer and eliminating background contamination from native-coat particles. We further show that RVdGenvA-CVS-N2c vectors produced using this system retain their enhanced retrograde-trafficking when compared with SAD-B19 vectors, allowing us to uncover undescribed cortico-hippocampal connections and to monitor activity in a cortical microcircuit of behaving animals. Along with new suites of AAV and RVdG-CVS-N2c vectors, developed to enable retrograde labeling from a wide range of neuronal populations and tailored for diverse experimental requirements, we present here an optimal system for mapping, manipulating and imaging of neuronal circuits.

Aging: Practice Interventions

2013 ◽  
Author(s):  
Lenard W. Kaye
Keyword(s):  
Social Work ◽  
Older Adult ◽  
Adult Population ◽  
Work Practice ◽  
Social Work Practice ◽  
Service Planning ◽  
Institutional Settings ◽  
Wide Range ◽  
Levels Of Service ◽  
Older Adult Population

Social workers address older adult issues at all levels of service planning, policy-making, and delivery and across a wide range of community and institutional settings. While various models of practice intervention with older adults exist, more recently the focus is on the integration of micro and macro strategies with an emphasis on strength-based perspectives to geriatric social work practice. The older adult population will expand dramatically and become increasingly culturally, racially, and ethnically diverse in the future and social work services will need to be sensitive to the variety of issues faced by a more heterogeneous and sophisticated older adult population.

scholarly journals PEGylated Amine-Functionalized Poly(ε-caprolactone) for the Delivery of Plasmid DNA

Materials ◽  
2020 ◽  
Vol 13 (4) ◽  
pp. 898 ◽  
Author(s):  
Amin Jafari ◽  
Nika Rajabian ◽  
Guojian Zhang ◽  
Mohamed Alaa Mohamed ◽  
Pedro Lei ◽  
...  
Keyword(s):  
Ethylene Glycol ◽  
Plasmid Dna ◽  
Viral Vectors ◽  
Viral Vector ◽  
Hydrolytic Stability ◽  
Poly Ethylene Glycol ◽  
Amine Functionalized ◽  
Structures And Properties ◽  
Wide Range ◽  
Poly Ethylene

As a promising strategy for the treatment of various diseases, gene therapy has attracted increasing attention over the past decade. Among various gene delivery approaches, non-viral vectors made of synthetic biomaterials have shown significant potential. Due to their synthetic nature, non-viral vectors can have tunable structures and properties by using various building units. In particular, they can offer advantages over viral vectors with respect to biosafety and cytotoxicity. In this study, a well-defined poly(ethylene glycol)-block-poly(α-(propylthio-N,N-diethylethanamine hydrochloride)-ε-caprolactone) diblock polymer (PEG-b-CPCL) with one poly(ethylene glycol) (PEG) block and one tertiary amine-functionalized cationic poly(ε-caprolactone) (CPCL) block, as a novel non-viral vector in the delivery of plasmid DNA (pDNA), was synthesized and studied. Despite having a degradable polymeric structure, the polymer showed remarkable hydrolytic stability over multiple weeks. The optimal ratio of the polymer to pDNA for nanocomplex formation, pDNA release from the nanocomplex with the presence of heparin, and serum stability of the nanocomplex were probed through gel electrophoresis. Nanostructure of the nanocomplexes was characterized by DLS and TEM imaging. Relative to CPCL homopolymers, PEG-b-CPCL led to better solubility over a wide range of pH. Overall, this work demonstrates that PEG-b-CPCL possesses a range of valuable properties as a promising synthetic vector for pDNA delivery.

scholarly journals In vivo genome editing in animals using AAV-CRISPR system: applications to translational research of human disease

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2153 ◽  
Author(s):  
Cia-Hin Lau ◽  
Yousin Suh
Keyword(s):  
Clinical Trials ◽  
Genome Editing ◽  
Viral Vectors ◽  
Ex Vivo ◽  
Guide Rna ◽  
Routes Of Administration ◽  
Cas9 Nuclease ◽  
Wide Range ◽  
Short Palindromic Repeat

Adeno-associated virus (AAV) has shown promising therapeutic efficacy with a good safety profile in a wide range of animal models and human clinical trials. With the advent of clustered regulatory interspaced short palindromic repeat (CRISPR)-based genome-editing technologies, AAV provides one of the most suitable viral vectors to package, deliver, and express CRISPR components for targeted gene editing. Recent discoveries of smaller Cas9 orthologues have enabled the packaging of Cas9 nuclease and its chimeric guide RNA into a single AAV delivery vehicle for robust in vivo genome editing. Here, we discuss how the combined use of small Cas9 orthologues, tissue-specific minimal promoters, AAV serotypes, and different routes of administration has advanced the development of efficient and precise in vivo genome editing and comprehensively review the various AAV-CRISPR systems that have been effectively used in animals. We then discuss the clinical implications and potential strategies to overcome off-target effects, immunogenicity, and toxicity associated with CRISPR components and AAV delivery vehicles. Finally, we discuss ongoing non-viral-based ex vivo gene therapy clinical trials to underscore the current challenges and future prospects of CRISPR/Cas9 delivery for human therapeutics.

Better Transportation Services for Older Persons

2003 ◽  
Vol 1843 (1) ◽  
pp. 105-112 ◽  
Author(s):  
Jon E. Burkhardt
Keyword(s):  
Public Transportation ◽  
Low Cost ◽  
Transportation Industry ◽  
Transportation Services ◽  
The Public ◽  
Long Run ◽  
Transportation Service ◽  
Wide Range ◽  
The One ◽  
Levels Of Service

Improvements to public transportation services are being made, or can be made, to offer better public transportation services for older travelers. Communities in which some of the most forward-looking ideas have been applied were examined. A number of short-term, low-cost improvements have been shown to be beneficial, but new perspectives are also needed. In the long run, multiple types of services, offered at varying prices, are needed to replace the “one size fits all” approach to public transportation with options that riders could choose on their own to fit the specific demands of individual days and trips. Shared-ride, demand-responsive services, dispatched and controlled through advanced technologies, could provide higher levels of service than now available and at higher levels of productivity and cost-effectiveness. Frequent, comfortable, affordable, spontaneous service to a wide variety of origins and destinations over a wide range of service hours is what seniors desire. A serious challenge for the public transportation industry will be finding ways of providing such services while collecting revenues that cover their costs. A key finding of this research is that the transportation service attributes most highly valued by older riders are not markedly different from those valued by other transit riders, so that improvements that would best serve older riders will also attract significant numbers of other riders.

scholarly journals Viral Vector Vaccines against Bluetongue Virus

2020 ◽  
Vol 9 (1) ◽  
pp. 42
Author(s):  
Luis Jiménez-Cabello ◽  
Sergio Utrilla-Trigo ◽  
Eva Calvo-Pinilla ◽  
Sandra Moreno ◽  
Aitor Nogales ◽  
...  
Keyword(s):  
Bluetongue Virus ◽  
Viral Vectors ◽  
Western Europe ◽  
Viral Vector ◽  
Vaccine Safety ◽  
Biting Midges ◽  
Livestock Disease ◽  
Prophylactic Measures ◽  
Wide Range ◽  
Inactivated Vaccines

Bluetongue virus (BTV), the prototype member of the genus Orbivirus (family Reoviridae), is the causative agent of an important livestock disease, bluetongue (BT), which is transmitted via biting midges of the genus Culicoides. To date, up to 29 serotypes of BTV have been described, which are classified as classical (BTV 1–24) or atypical (serotypes 25–27), and its distribution has been expanding since 1998, with important outbreaks in the Mediterranean Basin and devastating incursions in Northern and Western Europe. Classical vaccine approaches, such as live-attenuated and inactivated vaccines, have been used as prophylactic measures to control BT through the years. However, these vaccine approaches fail to address important matters like vaccine safety profile, effectiveness, induction of a cross-protective immune response among serotypes, and implementation of a DIVA (differentiation of infected from vaccinated animals) strategy. In this context, a wide range of recombinant vaccine prototypes against BTV, ranging from subunit vaccines to recombinant viral vector vaccines, have been investigated. This article offers a comprehensive outline of the live viral vectors used against BTV.

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