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Synthesis of Structure Based Vaccine Against Hepatitis C

C1.RESEARCH AREA
Molecular Biology, Bioinformatics and Biochemistry
D.PROJECT DIGEST
HCV is very common infectious disease all around the world (180 million people effected per year) and in Pakistan too and is a cause of chronic liver hepatitis C. It’s a small virus containing RNA as a genetic material. Over the course of evolution this virus has developed themselves and now we come across different viral genotypes all over the world. These viruses modify themselves structurally and functionally in an effort to evade from host immune response. Eleven different HCV genotypes are available. Drugs and vaccines are being developed all over the world but a major drawback is that these drugs and vaccines show genotype specific responses so drugs developed in other areas of world are not showing disease recovery in Pakistani hepatitis C patients. Currently IFN and ribavirin therapy is going on to cure HCV but it’s showing neutralization of virus in some patients but not in the other. So there is a need to develop such drugs here against specific Pakistani genotype i.e. 3a . HCV genotype found in Pakistan is type 3a so we are trying to explore the structure and then synthesis of structure based vaccine against HCV which show effective immunological responses against all viral strains. Our purpose is to do a genome wide study of all viral genotypes and then find out conserved regions present in all viral genotypes which would then be a target for vaccine development.
Project Details 1. PROJECT SUMMARY Virus of all different genotypes is collected from all over the world then a genome wide study will be performed to screen out conserved regions of genome and hence protein by using molecular biology techniques, bioinformatics tools and sequencing. These regions will then be targeted for vaccine development because these are important characteristic components of all viral genotypes. Antigenic potential of these conserved proteins will be determined by looking for antibodies present in blood of virally infected patients. We are thinking to target some of the viral polymerases which are required for viral RNA replication as well as structural glycoprotein present on viral surface.
2. PROPOSED GOALS/OBJECTIVES HYPOTHESIS/BASIS OF RESEARCH
Hypothesis is to develop vaccine against structural and functional region of HCV which show affectivity against all viral genotypes present all over the world.
RESEARCH OBJECTIVES
Sequencing of viral genomes of all genotypes
To find out conserved regions present in all genotypes
To root out viral infection
3. INTRODUCTION As HCV is to be reported as a chronic disease of liver effecting with its different genotypes existing all over the world. According to WHO report 2015 genotype 3 is most prevalent effecting 83.4 million people worldwide [1]. Genotype 3a is most prevalent in Pakistan[2]. These genotypes don’t differ dramatically in their structure but show different responsive behavior to drugs and vaccines. Such heterogeneity in their responsiveness is a major obstacle to develop a vaccine which is able to neutralize all types of these viral genotypes. But science is still far away. For global protection of Hepatitis C Virus a vaccine is needed able to neutralize all genotypes. One of the vaccines developed against Hepatitis C is reported but it is specific for genotype1a and 1b. We are therefore in a need to synthesize vaccine against genotype 3a, most prevent in Pakistan.
For this purpose we are trying to conduct a genome wide study of all viral strains and trace their conserved regions in their genome. Then antigenic potential of these conserved regions’ll be determined by looking for antibodies present in the blood of chronically infected HCV patients. These antigenic regions’ll then be studied and characterized by using different molecular biology techniques. These antigenic regions used as vaccine to mount antibody response in healthy individuals so whenever they come across with virus in their future life they would be able to produce a stronger response against that virus and don’t let them to grow.
This vaccine will be able to neutralize the disease burden not only against 3a genotype but all other genotypes too because we’ll target those regions which are conserved in al viral genotypes. Although drug against this hepatitis C virus is now available which is effective against all strains of viruses but due to its high economic cost it isn’t in the range of poor community in our country. So it’s good to make an effort to root out this devastating disease. Our struggle to develop vaccine is in line with this effort.
4 A. BACKGROUND OF THE RESEARCH PROBLEMS TO BE ADDRESSED A comprehensive and up-to-date literature survey clearly highlighting the existing gaps and what new information will be added to the existing pool of knowledge.
As HCV is to be reported as a chronic disease of liver effecting with its different genotypes existing all over the world. Genotype 3a is most prevalent in Pakistan [2]. Different drugs are available against different viral strains. Sofobuvir is reported to be effective against HCV type 2

The Ethics of Human Enhancement

Bor Shin Chee
Human Enhancement
The term ‘human enhancement’ embraces a range of approaches to improve aspects of human function such as memory, hearing and mobility to improve human performance, hence raising these function to a level considered to be beyond the existing human range.
Human enhancement categorized into particular areas: life extension, physical enhancement, cognitive enhancement, enhancement of mood or personality, and pre- and perinatal interventions. There are some existing technologies which can temporarily or permanently dealing with the current limitations of the human body via natural or artificial means: the use of reproductive technology, for example, embryo selection by pre-implantation genetic diagnosis, cytoplasmic transfer, In vitro generated gametes; the physical enhancement technologies such as plastic surgery, doping drugs, organ replacement; the enhancement of cognition, memory or concentration technologies by using nootropics, drugs, and neurostimulation devices. In addition, there are some emerging technologies such as human genetic engineering, neural implants, nanomedicine, brain–computer interface, neurotechnology and gene therapy which have the potential for human enhancement. These novel enhancement technologies bring significant implications for individuals and society.
Human enhancement is said to be the convergence of nanotechnology, biotechnology, information technology and cognitive science (NBIC) to change the human condition. There will be lots of ethical issues coming out when a novel technology emerged.
“Designer” babies
Designer babies refers to children that were genetically engineered in the uterus to possess certain physical appearance and skill or no genetic disorder and abnormalities. Thus, human enhancement is roughly synonymous with human genetic engineering which capable to lower a child’s’ risk of developing many disorders and illnesses, as well as being able to choose gender, eye color, hair, height, intelligence and other qualities.
Designer babies are made via the process of in-vitro fertilization where the embryo is first removed from a female and sperm from a male. “test-tube babies” is then fertilized on a petri dish. At this stage, certain desired qualities can be choose to obtain in the embryo in a lab. Then followed by placing it again into a female womb to finish development. Hence during these pre-implantation genetic diagnosis, a scientist could state what physical characteristics a child will grow to have, along with whether or not this child is at risk of developing certain genetic disorders such as Huntington’s disease, Down syndrome and etc.
There is some controversy over the idea of “designer babies.” Many people argue that it is unethical and unnatural to create a baby the way you desired to have, while others argue that this technology could stop certain genetic diseases in babies before they born.
Some disagree about this idea because parents might have superficial purposes by using this technology for purposely seeking out certain characteristics; such as requesting a blonde haired, blue eyed baby for appearance concerns only. This “Designer” babies who probably had enhanced their appearance, intelligence and etc would widen the gap between designer andnon-designerbabies in society. The best of the best of students or professors are tenure for titles, scholarships, and many other advantages that are now, thanks to designer babies, reducing the opportunities or even unavailable to the others. There is also a negative consequence for the job-seekers, the ‘designer’ babies would outcompete someone who is not designed, causing the “non-designer” children to miss opportunities because employers most likely will hire the “optimum” candidates. Finally could create prejudice between “Designer” and “non-designer” children in the society, humans should have to be equal to one another. If this technology continually developed, individuality will be slighted, everyone will be relatively similar because most people had these optimum characteristics.
Being able to see whether or not a child has a genetic disease, and also working on fixing certain degenerative diseases through genetic alterations would give the parents time to prepare for the road ahead. However, when those same doctors start saying that with an extra paying, customers can change the sex of their child, people began questioning the business. The wealthy would be the first adopters of the technology, the process is not cheap that not everyone would be able to afford such innovation, thus creating an even wider gap between the have and have-nots. The parents who cannot afford might cause guilty for their children.
According to ASRM, only 24% of the time the genetically modify process is successful. If it is not done carefully, the embryo could be accidentally terminated. 10-24 embryos are taken from the owner at one time and experimented on but only one is selected to be implanted, and the others are immediately discarded. In this condition, that’s a range of 9- 23 abortions, all for one “perfect” baby, no woman should have the right to selective abortion. Only 24% of are successful given the desired results, which leave 76% of mistakes and unsuccessful results. Is this 24% chance of a healthy baby worth the risk?
Besides, the technology has not been proven 100% completely safe, for the embryo or the mother, it contained scientific uncertainty as the technology is only in the experimental stages at this phase. It still cannot be confirmed that whether genetically modifying the babies will affect the gene pool which might cause difficulties later on throughout the baby’s family tree. Some other concern are that genetic modification induces gene at random places in the genome. It could just disrupt the function of another genome crucial for survival. Many gene have more than one affect that can be affected by pre-implantation. Multiple gene influence many of the trait that we may want to select, we are unlikely to find single gene responsible for a certain function such as IQ. For example, a gene that controls intelligence could also control anger management, so you could end up with a genius, but very angry child. This new technology create a way to prevent the disease, most of also replacing certain gene while the other being enhancement of certain more desirable trait. Some argument against designer babies conclude that genetic enhancement connect too close with eugenics program promoted by NAZI in the world war two.
Another complaint about Designer babies is they are not naturally born which mean that that is not the way a child was made. Many people see genetic altering as morally wrong because they explain it as not accepting your child the way he or she was. If the child found out that their parents picked out how they look or act, it might cause conflict between the child and parents. For example, parents had picked traits to make their child possess athletic abilities and the child does not make it onto the soccer team when they had grew up, it might set the parents up for disappointment with the fact that they paid for a trait that “didn’t pay off” and also lead to the child being hurt.
The above issue is related to human right. The designer baby cannot consent to having his/her body altered, therefore some do not believe it is right because parents do not “own” their children. Adults have the fundamental freedom to choose whether or not they want to do that with their bodies, as long as it does not hurt others, but children are children. The issue of parental responsibilities and rights associated with decisions to enhance children is concerned, whether directly after the child is born or indirectly through germ-line enhancements. If parents decide to enhance children through genetic modification, it is said that they have already been making a crucial decision about the capabilities of their children that may be irreversible and limit their children’s future choices and opportunities. Will the child agree with the choices of what their parents had chosen for them when he or she is older?
Even though there are many issues of if genetically modifying babies is ethical and for the moral reason, there are several positives to this type of technology. Since this treatment has been established, some people might use this process to have children that will be an exact match to an older sibling who is terminally ill and by this way it can provide the opportunity for saving someone’s life because he or she received organs, blood, bone marrow and other such body parts.
Parents have the “right” reasons to genetically modify their baby to eliminate mitochondrial disorders, prevent genetic diseases such as Spinal Muscular Atrophy, Alzheimer’s, and many others or reduces risk of inherited medical conditions such as anemia, cancer, diabetes and etc which allows their child having a healthy life as well as increasing their children life span up to 30 years. Additionally, the scientists can help infertile women to give birth using in-vitro fertilization. It gave the higher chances of success when comparing with natural conception. Government does not have the right to control means of citizens’ reproduction and the right to prohibit giving the child genes that the parent does not carry, creating a quick adaptation to any environment.
Although not all the kinks in this novel developing technology are fixed, with more clinical trials and experimentation, it has the potential to be a very promising to provide a better understanding of genetics for genealogists and biologists. Hence, the ethical viewpoints should not cease the advancement of technology.
In my opinion, according to my study about the ethics of human enhancement, designer babies is one of the best thing that children are enhanced with particular abilities or appearance prior to their birth. I knew that with the advancements of all scientific and technological, there is always exist of ethical questions behind the hopes for these procedures, but we should keep up with modern technologies. Human enhancement projects help thousands or even millions of people to live better.
References
Barnard, E., Schrading, J., Fluornoy, K. and Brown, I. (2013) The Ethics of “Designer Babies”. [Online]. Available at: https://designerbabiesethics.wordpress.com/about/ [Accessed 3 April 2015].
Bostrom, N.

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