Vector control is the principal method available for controlling many VBDs—both historically and today. Moreover, for some diseases, such as dengue (a vaccine is licensed but is not widely used due to safety concerns [ 10 ]), chikungunya, Zika, and West Nile disease, vector control is currently the only method available to protect populations.
Why do we need vector control and treatment?
Both prevention through vector control and treatment are needed to protect populations. As the impacts of disease and virus are devastating, the need to control the vectors in which they carried is prioritized. Vector control in many developing countries can have tremendous impacts as it reduces mortality rates, especially among infants.
What is a vector in gene therapy?
The system used to deliver genetic material is known as a vector. Think of a vector as a microscopic delivery truck that transports packages (genetic material) to specific locations (target cells). There are two types of vectors, viral and non-viral. Viral vectors are currently a delivery vehicle used in FDA-approved gene therapies.
What tools have been successfully applied to vector control?
Throughout the history of vector control, a range of different tools were successfully applied. It is striking, however, that environmental management such as drainage and filling and larviciding come up repeatedly—particularly pre 1940—but were less common thereafter (as noted by Keiser and colleagues for malaria control [22]).
What are the applications of viral vectors?
Viral vectors are also explored for use in gene and cell therapy and as basis for prophylactic and therapeutic vaccines. In gene therapy, viral vectors can be used for delivery of functional genes to replace defective genes to cure genetic disorders.
What is the vector used in gene therapy?
1 Adenovirus. Adenoviruses are the most widely used vectors in gene therapy, with more than 500 clinical assays. There are almost 60 different adenoviral serotypes currently reported in human populations, and the majority of adenoviral vectors derive from serotypes Ad2 and Ad5.
What's an advantage of using viruses as a vector for gene therapy?
Benefits and advantages of using the Adeno-Associated Virus as the vector in gene therapy trials include integration into host genome, no viral genes, able to transduce cells not actively dividing, wide range of host cells, and they are non-inflammatory and non-pathogenic.
What are retroviral vectors used for?
Retroviral vectors have been used to introduce a drug susceptibility or “suicide” gene, such as herpes simplex thymidine kinase (TK), to target cells. When the patient is treated with a particular drug, such as gancyclovir, the target cells containing TK are killed selectively.
What diseases can be treated with gene therapy?
Gene therapy holds promise for treating a wide range of diseases, such as cancer, cystic fibrosis, heart disease, diabetes, hemophilia and AIDS. Researchers are still studying how and when to use gene therapy. Currently, in the United States, gene therapy is available only as part of a clinical trial.
What is the difference between a virus and a vector?
In viral vector vaccines, spike protein DNA is placed inside a modified version of a different virus that doesn't cause illness. This non-harmful virus delivers the DNA instructions to your cells – this virus is called the vector.
What are some examples of viral vector vaccines?
Viral vector vaccines use a modified version of a different virus as a vector to deliver protection. Several different viruses have been used as vectors, including influenza, vesicular stomatitis virus (VSV), measles virus, and adenovirus, which causes the common cold.
Why are retroviruses used in gene therapy?
You can use retroviruses for gene therapy, because you can firstly make viral particles with the genome inside that only contain your favorite gene, and you can then infect your target cells. Those infected cells will only be modified by the insertion of your target gene into their chromatin. That's great.
What is retroviral infection?
Retroviruses are a family of viruses that are grouped together based on how they are structured and how they replicate within a host. Besides human immunodeficiency virus (HIV), the virus that causes AIDS, there a two other retroviruses that can cause human illness.
What is the purpose of gene therapy?
Human gene therapy seeks to modify or manipulate the expression of a gene or to alter the biological properties of living cells for therapeutic use 1. Gene therapy is a technique that modifies a person's genes to treat or cure disease.
Which disease was first successfully cured by gene therapy?
The first patient to be treated with gene therapy was a four year old girl treated at the NIH Clinical Center in 1990. She had a congenital disease called adenosine deaminase (ADA) deficiency which severely affects immunity and the ability to fight infections.
What 3 types of vectors can be used to complete gene therapy?
Viral vectors: adenoviral, retroviral lentiviral and AAVs To do this, viruses introduce genetic material into host cells in order to replicate, making them fantastic resources for gene therapy.
What is the most common retroviral vector used in gene therapy?
For example, the most popular retroviral vector for use in gene therapy trials has been the lentivirus Simian immunodeficiency virus coated with the envelope proteins, G-protein, from Vesicular stomatitis virus. This vector is referred to as VSV G-pseudotyped lentivirus, and infects an almost universal set of cells.
What is a transfer construct in a vector?
Replication-defective vectors always contain a “transfer construct”. The transfer construct carries the gene to be transduced or “transgene”. The transfer construct also carries the sequences which are necessary for the general functioning of the viral genome: packaging sequence, repeats for replication and, when needed, priming of reverse transcription. These are denominated cis-acting elements, because they need to be on the same piece of DNA as the viral genome and the gene of interest. Trans-acting elements are viral elements, which can be encoded on a different DNA molecule. For example, the viral structural proteins can be expressed from a different genetic element than the viral genome.
What is gene therapy?
Gene therapy utilizes the delivery of DNA into cells, which can be accomplished by several methods, summarized below. The two major classes of methods are those that use recombinant viruses (sometimes called biological nanoparticles or viral vectors) and those that use naked DNA or DNA complexes (non-viral methods).
Why use synthetic oligonucleotides?
Oligonucleotides. The use of synthetic oligonucleotides in gene therapy is to deactivate the genes involved in the disease process. There are several methods by which this is achieved. One strategy uses antisense specific to the target gene to disrupt the transcription of the faulty gene.
Does gene therapy help with SCID?
All but one of these children responded well to conventional anti-leukemia treatment. Gene therapy trials to treat SCID due to deficiency of the Adenosine Deaminase ( ADA) enzyme (one form of SCID) continue with relative success in the USA, Britain, Ireland, Italy and Japan.
Why are nonviral vectors used in gene therapy?
The use of nonviral vectors in gene therapy has increased over the past decade, largely in part due to several key advantages over viral vectors. Firstly, nonviral vectors are generally less immunogenic than viral vectors, which greatly improves treatment tolerance and allows for repeat administration of the compound without the immune system rejecting the therapy. In addition, nonviral vectors have the advantage of increased genetic-carrying capacity, thus allowing for multiple gene delivery and more complicated treatment designs ( Mintzer and Simanek, 2008 ). Finally, nonviral vectors are generally easier to mass-produce, compared to viral vectors ( Pack et al., 2005 ). Despite these advantages, nonviral vectors have a fundamental deficiency in delivery efficiency ( Putnam, 2006; Yin et al., 2014 ). Viral vectors have evolved over hundreds of millions of years with the sole drive to deliver their genetic material into prokaryotic or eukaryotic cell types. Therefore, there is a significant engineering difficulty when designing nonviral vector systems to achieve comparable gene transfer efficiency. Nevertheless, researchers continue to approach this problem and develop novel synthetic vectors. For example, Abu-Rub et al. (2016) explored the use of siRNA as a means to silence XT-1, the rate-limiting enzyme involved in CSPG synthesis during spinal cord injuries. With the use of this siRNA, there was a 65% silencing rate in Neu7 astrocytes, which conferred a reduction of expression of CSPGs.
What are retroviral vectors used for?
Retroviral vectors#N#The commonly used and most employed vector in gene therapy is the retroviral vector. They are used in both somatic and germline gene therapy. They contain three genomes such as gag for encoding viral proteins, pol for entering target cells, and env for enveloping the protein of the virus, which identify the receptors in the host cell and enable the viral entry. Retroviruses have an ability to cross the nuclear pores of mitotic cells, and this makes them useful in situ treatment. They are used in ex vivo treatment, as they can linearly integrate into the host cell genome. They have been demonstrated in familial hyperlipidemia gene therapy and tumor vaccination ( Mali, 2013 ).
What is AAV vector?
AAV has shown great promise as a gene therapy vector in multiple aspects of preclinical and clinical applications. Many developments including new serotypes as well as self complementary vectors are now entering the clinic. With these ongoing vector developments in addition to new methods such as directed evolution, continued effort has been focused on scalable manufacturing processes that can efficiently generate high titer, highly pure, and potent quantities of rAAV vectors. Advances and novel approaches in rAAV production have been made recently that have allowed some laboratories to move away from production using adherent HEK293 cells and move toward scalable technologies. Three of these novel approaches are (1) development of HEK293 cell lines that can grow in serum-free suspension conditions, (2) the baculovirus expression vector system (BEVS) utilizing Spodoptera frugiperda (Sf9) cells, and (3) the dual rHSV infection system of suspension baby hamster kidney (BHK) cells. Each of these systems shows promise as the next generation scalable production platform for GMP manufacturing of rAAV vectors for clinical applications.
How do retroviruses work?
They produce faithful transmission of the transgene into the transduced cell progeny by integrating their complementary DNA into the host genome during their life cycle (Miller, 1997; Verma and Somia, 1997 ). Retroviruses enter mammalian cells through specific cell surface receptors, which limit their range of infectivity. However, the host range can be expanded and the stability of the virus may be substantially increased through the modifications of viral envelope that can serve to redirect receptor interactions. After entry into mammalian cells, the RNA genome is reverse-transcribed into double-stranded DNA provirus, which is incorporated into a preintegration nucleoprotein complex (PIC). The PIC must then be transferred into the nucleus for integration of the provirus into the host genome. However, the PIC of some viruses, such as the Moloney murine leukemia virus (MoMuLV), does not pass through intact nuclear membranes. To overcome this barrier, mitosis-associated dissolution of nuclear envelope is required for the integration of the MoMuLV provirus ( Fassati and Goff, 1999; Elis et al., 2012 ). This limits the efficiency of these viruses in transferring genes into hepatocytes, which are normally quiescent in vivo. Interestingly, however, long-term correction of hemophilia A using retroviral vectors expressing human factor VIII was reported in newborn, factor VIII-deficient mice ( Xu et al., 2007 ), suggesting that retrovirus-based gene therapy can be achieved for liver-specific applications.
What is the most common vector for a virus?
Among the simple retroviruses (oncogenic retroviruses), the murine leukemia virus is most commonly used as a vector in gene therapy while, in the complex category, the most commonly used vector is lentivirus . Retroviridae are enveloped viruses of a diameter of 80–100 nm. The envelope is a lipid bilayer derived from the host cell membrane that additionally contains virus-encoded glycoproteins. The genome is a linear, single-stranded RNA of 7–12 kb in length. The genome of simple retroviruses contains three major coding segments ( gag, pol, env) and one small coding domain ( pro ). Complex retroviruses such as lentivirus carry six additional genes (two regulatory and four accessory genes).
Why is retrovirus used in gene therapy?
Retrovirus has been considered to be an ideal viral vector for gene therapy, because the viral genome is stably integrated into the chromosome. In fact, retroviral vectors have been the most extensively used gene therapy vectors in the early stages of clinical trials. Currently, the use of retroviral vectors is limited to research purposes only. Nonetheless, the retroviral vectors are widely used in laboratories for the purpose of gene expression. The underlying principle of the retroviral vector is the same, whether it is for gene therapy or for basic research.
What is the role of retrovirus in gene therapy?
For gene therapy purposes, all viral genes of the retrovirus or lentivirus genome are deleted, making these vectors replication-defective and provides space for insertion of genes of interest. Compared to adenovirus and AAV, retrovirus-based vectors show relatively low transduction efficiency in vivo.
What is vector therapy?
Vectors. In gene therapy, genetic material from outside the body needs to get inside the nucleus. Currently, the only way this can happen is through the use of viral or non-viral vectors. You can learn more about vectors in this part of genehome.
What was the first viral vector used in gene therapy?
The first viral vector used in gene therapy was based on adenovirus, which is a virus that causes the common cold. However, some adenoviral vectors (AdV) were found to trigger strong, potentially dangerous, immune reactions in patients. Further research in the use of AdV is being explored. 1, 8
What is a vector that is not needed for delivery of genetic material?
The parts of the viral genome that are not needed for delivery of genetic material are never used. This is so that the vector does not produce the infection that would be caused by the complete virus. Here's an example of how a vector is created from a virus: Let's use a lentiviral vector as our example.
How many genes are in the HIV vector?
The HIV genome is made up of 9 genes and every single gene is required to cause disease. To make the vector, scientists select 3 or 4 different genes from the blueprint of the viral genome.
When were lentiviral vectors first used?
Lentiviral vectors. Lentiviral vectors (LVV) were first explored in gene therapy in the 1980s and became a viable gene therapy technology that evolved quickly in the mid-1990s. Lentiviruses are a species of. retrovirus.
What is the final viral vector?
The final viral vector is like a delivery truck that has updated its contents. The delivery truck just needs the correct address to deliver the new load. Once the genetic material carried by the vector has been delivered to the host cell/tissue, it can help deliver the transgene (or gene of interest) to the nucleus.
What is the name of the vehicle that carries genetic material?
The vehicle that carries this genetic material is known as a vector.
What is the purpose of viral vectors?
Viral vectors are also explored for use in gene and cell therapy and as basis for prophylactic and therapeutic vaccines. In gene therapy, viral vectors can be used for delivery ...
Why should vectors be modified?
Vectors should be modified to provide safe handling (no production of new virions in host) and low toxicity (no effect of the physiology of the normal host cell). They should also be stable (no rearrangement of genome), and for manufacturing, ...
How does VACV work?
VACV is a double-stranded DNA virus that enters its host cell by cell fusion. Its large genome (185 kilobases) tolerates insertions of foreign DNA fragments of more than 25 kilobases , creating an opportunity for use of VACV in vaccines with large or even several antigens. Poxviruses have also been modified and tested as oncolytic therapies.
What is AAV in biology?
AAV is a single-stranded DNA virus that can infect both actively dividing and non-dividing cells of humans and some other primates. It can integrate into the genome of the host cell but mostly, as adenovirus, AAV replicate without incorporating its genome into the host cell chromosome. As opposed to adenovirus, which is a larger virus that can deliver DNA inserts of up to 36 kilobases, AAV is a small virus that can only deliver smaller inserts of up to 5 kilobases. AAV is mainly used for gene therapy.
What is viral vector?
In gene therapy, viral vectors can be used for delivery of functional genes to replace defective genes to cure genetic disorders. As a vaccine platform, viral vectors can be used for expression and presentation of pathogenic antigens to induce an immune response by mimicking a natural infection. Viral vectors can also be used in oncolytic therapies ...
What are some examples of viral vector systems?
Example of viral vector systems are retrovirus, lentivirus, poxvirus, adenovirus, and adeno-associated virus.
Is lentivirus a retrovirus?
LENTIVIRUS. Lentiviruses are a subclass of retroviruses, but in contrast to other retroviruses, lentiviruses can integrate into the genome of non-dividing cells. As retrovirus vectors, lentivirus vectors never include genes for replication.
Why is vector control important?
For diseases where there is no effective cure, such as Zika virus, West Nile fever and Dengue fever, vector control remains the only way to protect human populations. However, even for vector-borne diseases with effective treatments the high cost of treatment remains a huge barrier to large amounts of developing world populations.
What is vector control?
Vector control is any method to limit or eradicate the mammals, birds, insects or other arthropods (here collectively called " vectors ") which transmit disease pathogens. The most frequent type of vector control is mosquito control using a variety of strategies.
What is vector control district?
For example, in California, the Greater Los Angeles County Vector Control District is a special district set up by the state to oversee vector control in multiple cities.
What is integrated vector management?
The World Health Organization therefore recommends "Integrated Vector Management" as the process for developing and implementing strategies for vector control.
How to reduce the risk of infection?
Reducing contact. Limiting exposure to insects or animals that are known disease vectors can reduce infection risks significantly. For example, bed nets, window screens on homes, or protective clothing can help reduce the likelihood of contact with vectors.
Can larvicides be used for mosquitoes?
For example, larvicides can be used in mosquito breeding zones; insecticides can be applied to house walls or bed nets, and use of personal repellents can reduce incidence of insect bites and thus infection. The use of pesticides for vector control is promoted by the World Health Organization (WHO) and has proven to be highly effective.
What is the benefit of a viral vector?
The benefit of viral vector vaccines, like all vaccines, is those vaccinated gain protection without ever having to risk the serious consequences of getting sick with COVID-19. Learn more about getting your vaccine. Viral vector vaccines are among the COVID-19 vaccines authorized for use in the United States.
How do vectors work?
How They Work. Viral vector vaccines use a modified version of a different virus (the vector) to deliver important instructions to our cells. First, the vector ( not the virus that causes COVID-19, but a different, harmless virus) will enter a cell in our body and then use the cell’s machinery to produce a harmless piece ...
When were viral vectors invented?
Scientists began creating viral vectors in the 1970s. Besides being used in vaccines, viral vectors have also been studied for gene therapy, to treat cancer, and for molecular biology research. For decades, hundreds of scientific studies of viral vector vaccines have been done and published around the world.
