Current Status of Gene Therapy Research

Current Status of Gene Therapy Research Genes, which are carried on chromosomes, are the basic physical and functional units of heredity. Genes are specific sequences of bases that encode instructions on how to make proteins. Although genes get a lot of attention, its the proteins that perform most life functions and even make up the majority of cellular structures. When genes are altered so that the encoded proteins are unable to carry out their normal functions, genetic disorders can result. Gene therapy is a technique for correcting defective genes responsible for disease development. Researchers may use one of several approaches for correcting faulty genes: A normal gene may be inserted into a nonspecific location within the genome to replace a nonfunctional gene. This approach is most common. An abnormal gene could be swapped for a normal gene through homologous recombination. The abnormal gene could be repaired through selective reverse mutation, which returns the gene to its normal function. The regulation (the degree to which a gene is turned on or off) of a particular gene could be altered. How does gene therapy work? In most gene therapy studies, a normal gene is inserted into the genome to replace an abnormal, disease-causing gene. A carrier molecule called a vector must be used to deliver the therapeutic gene to the patients target cells. Currently, the most common vector is a virus that has been genetically altered to carry normal human DNA. Viruses have evolved a way of encapsulating and delivering their genes to human cells in a pathogenic manner. Scientists have tried to take advantage of this capability and manipulate the virus genome to remove disease-causing genes and insert therapeutic genes. Target cells such as the patients liver or lung cells are infected with the viral vector. The vector then unloads its genetic material containing the therapeutic human gene into the target cell. The generation of a functional protein product from the therapeutic gene restores the target cell to a normal state. See adiagram  depicting this process. Some of the different types of viruses used as gene therapy vectors: Retroviruses   A class of viruses that can create double-stranded DNA copies of their RNA genomes. These copies of its genome can be integrated into the chromosomes of host cells. Human immunodeficiency virus (HIV) is a retrovirus. Adenoviruses   A class of viruses with double-stranded DNA genomes that cause respiratory, intestinal, and eye infections in humans. The virus that causes the common cold is an adenovirus. Adeno-associated viruses   A class of small, single-stranded DNA viruses that can insert their genetic material at a specific site on chromosome 19. Herpes simplex viruses   A class of double-stranded DNA viruses that infect a particular cell type, neurons. Herpes simplex virus type 1 is a common human pathogen that causes cold sores. Besides virus-mediated gene-delivery systems, there are several nonviral options for gene delivery. The simplest method is the direct introduction of therapeutic DNA into target cells. This approach is limited in its application because it can be used only with certain tissues and requires large amounts of DNA. Another nonviral approach involves the creation of an artificial lipid sphere with an aqueous core. This liposome, which carries the therapeutic DNA, is capable of passing the DNA through the target cells membrane. Therapeutic DNA also can get inside target cells by chemically linking the DNA to a molecule that will bind to special cell receptors. Once bound to these receptors, the therapeutic DNA constructs are engulfed by the cell membrane and passed into the interior of the target cell. This delivery system tends to be less effective than other options. Researchers also are experimenting with introducing a 47th (artificial human) chromosome into target cells. This chromosome would exist autonomously alongside the standard 46 not affecting their workings or causing any mutations. It would be a large vector capable of carrying substantial amounts of genetic code, and scientists anticipate that, because of its construction and autonomy, the bodys immune systems would not attack it. A problem with this potential method is the difficulty in delivering such a large molecule to the nucleus of a target cell. What is the current status of gene therapy research? The Food and Drug Administration (FDA) has not yet approved any human gene therapy product for sale. Current gene therapy is experimental and has not proven very successful in clinical trials. Little progress has been made since the first gene therapy clinical trial began in 1990. In 1999, gene therapy suffered a major setback with the death of 18-year-old Jesse Gelsinger. Jesse was participating in a gene therapy trial for ornithine transcarboxylase deficiency (OTCD). He died from multiple organ failures 4 days after starting the treatment. His death is believed to have been triggered by a severe immune response to the adenovirus carrier. Another major blow came in January 2003, when the FDA placed a temporary halt on all gene therapy trials using retroviral vectors in blood stem cells. FDA took this action after it learned that a second child treated in a French gene therapy trial had developed a leukemia-like condition. Both this child and another who had developed a similar condition in August 2002 had been successfully treated by gene therapy for X-linked severe combined immunodeficiency disease (X-SCID), also known as bubble baby syndrome. FDAs Biological Response Modifiers Advisory Committee (BRMAC) met at the end of February 2003 to discuss possible measures that could allow a number of retroviral gene therapy trials for treatment of life-threatening diseases to proceed with appropriate safeguards. In April of 2003 the FDA eased the ban on gene therapy trials using retroviral vectors in blood stem cells. What factors have kept gene therapy from becoming an effective treatment for genetic disease? Short-lived nature of gene therapy   Before gene therapy can become a permanent cure for any condition, the therapeutic DNA introduced into target cells must remain functional and the cells containing the therapeutic DNA must be long-lived and stable. Problems with integrating therapeutic DNA into the genome and the rapidly dividing nature of many cells prevent gene therapy from achieving any long-term benefits. Patients will have to undergo multiple rounds of gene therapy. Immune response   Anytime a foreign object is introduced into human tissues, the immune system is designed to attack the invader. The risk of stimulating the immune system in a way that reduces gene therapy effectiveness is always a potential risk. Furthermore, the immune systems enhanced response to invaders it has seen before makes it difficult for gene therapy to be repeated in patients. Problems with viral vectors   Viruses, while the carrier of choice in most gene therapy studies, present a variety of potential problems to the patient toxicity, immune and inflammatory responses, and gene control and targeting issues. In addition, there is always the fear that the viral vector, once inside the patient, may recover its ability to cause disease. Multigene disorders   Conditions or disorders that arise from mutations in a single gene are the best candidates for gene therapy. Unfortunately, some the most commonly occurring disorders, such as heart disease, high blood pressure, Alzheimers disease, arthritis, and diabetes, are caused by the combined effects of variations in many genes. Multigene or multifactorial disorders such as these would be especially difficult to treat effectively using gene therapy. For more information on different types of genetic disease, see  Genetic Disease Information. What are some recent developments in gene therapy research? Nanotechnology + gene therapy yields treatment to torpedo cancer. March, 2009. The School of Pharmacy in London is testing a treatment in mice, which delivers genes wrapped in nanoparticles to cancer cells to target and destroy hard-to-reach cancer cells. Read  BBC article. Results of worlds first gene therapy for inherited blindness show sight improvement. 28 April 2008. UK researchers from the UCL Institute of Ophthalmology and Moorfields Eye Hospital NIHR Biomedical Research Centre have announced results from the worlds first clinical trial to test a revolutionary gene therapy treatment for a type of inherited blindness. The results, published today in the New England Journal of Medicine, show that the experimental treatment is safe and can improve sight. The findings are a landmark for gene therapy technology and could have a significant impact on future treatments for eye disease. Read  Press Release. Previous information on this trial (May 1, 2007): A team of British doctors from Moorfields Eye Hospital and University College in London conduct first human gene therapy trials to treat Lebers congenital amaurosis, a type of inherited childhood blindness caused by a single abnormal gene. The procedure has already been successful at restoring vision for dogs. This is the first trial to use gene therapy in an operation to treat blindness in humans. See  Doctors Test Gene Therapy to Treat Blindness  at www.reuters.com.   A combination of two tumor suppressing genes delivered in lipid-based nanoparticles drastically reduces the number and size of human lung cancer tumors in mice during trials conducted by researchers from The University of Texas M. D. Anderson Cancer Center and the University of Texas Southwestern Medical Center. See  Dual Gene Therapy Suppresses Lung Cancer in Preclinical Test  at www.newswise.com (January 11, 2007). Researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, successfully reengineer immune cells, called lymphocytes, to target and attack cancer cells in patients with advanced metastatic melanoma. This is the first time that gene therapy is used to successfully treat cancer in humans. See  New Method of Gene Therapy Alters Immune Cells for Treatment of Advanced Melanoma  at www.cancer.gov (August 30, 2006).   Gene therapy is effectively used to treat two adult patients for a disease affecting nonlymphocytic white blood cells called myeloid cells. Myeloid disorders are common and include a variety of bone marrow failure syndromes, such as acute myeloid leukemia. The study is the first to show that gene therapy can cure diseases of the myeloid system. See  Gene Therapy Appears to Cure Myeloid Blood Diseases In Groundbreaking International Studyat www.cincinnatichildrens.org (March 31, 2006).   Gene Therapy cures deafness in guinea pigs. Each animal had been deafened by destruction of the hair cells in the cochlea that translate sound vibrations into nerve signals. A gene, called  Atoh1,  which stimulates the hair cells growth, was delivered to the cochlea by an adenovirus. The genes triggered re-growth of the hair cells and many of the animals regained up to 80% of their original hearing thresholds. This study, which many pave the way to human trials of the gene, is the first to show that gene therapy can repair deafness in animals. See  Gene Therapy is First Deafness Cure  at NewScientist.com (February 11, 2005). University of California, Los Angeles, research team gets genes into the brain using liposomes coated in a polymer call polyethylene glycol (PEG). The transfer of genes into the brain is a significant achievement because viral vectors are too big to get across the blood-brain barrier. This method has potential for treating Parkinsons disease. See  Undercover Genes Slip into the Brain  at NewScientist.com (March 20, 2003). RNA interference or gene silencing may be a new way to treat Huntingtons. Short pieces of double-stranded RNA (short, interfering RNAs or siRNAs) are used by cells to degrade RNA of a particular sequence. If a siRNA is designed to match the RNA copied from a faulty gene, then the abnormal protein product of that gene will not be produced. See  Gene Therapy May Switch off Huntingtons  at NewScientist.com (March 13, 2003). New gene therapy approach repairs errors in messenger RNA derived from defective genes. Technique has potential to treat the blood disorder thalassaemia, cystic fibrosis, and some cancers. See  Subtle Gene Therapy Tackles Blood Disorder  at NewScientist.com (October 11, 2002). Gene therapy for treating children with X-SCID (sever combined immunodeficiency) or the bubble boy disease is stopped in France when the treatment causes leukemia in one of the patients. See  Miracle Gene Therapy Trial Halted  at NewScientist.com (October 3, 2002). Researchers at Case Western Reserve University and Copernicus Therapeutics are able to create tiny liposomes 25 nanometers across that can carry therapeutic DNA through pores in the nuclear membrane. See  DNA Nanoballs Boost Gene Therapy  at NewScientist.com (May 12, 2002).   Sickle cell is successfully treated in mice. See  Murine Gene Therapy Corrects Symptoms of Sickle Cell Disease  from March 18, 2002, issue of  The Scientist. What are some of the ethical considerations for using gene therapy? Some Questions to Consider What is normal and what is a disability or disorder, and who decides?   Are disabilities diseases? Do they need to be cured or prevented?   Does searching for a cure demean the lives of individuals presently affected by disabilities?   Is somatic gene therapy (which is done in the adult cells of persons known to have the disease) more or less ethical than germline gene therapy (which is done in egg and sperm cells and prevents the trait from being passed on to further generations)? In cases of somatic gene therapy, the procedure may have to be repeated in future generations.   Preliminary attempts at gene therapy are exorbitantly expensive. Who will have access to these therapies? Who will pay for their use?

Health Development in Africa Essay

Throughout the world there is a growing concern about health as it is regarded as an essential part of the sustainable human development efforts. The growing importance of the health of the population is being highlighted in the economic circles, the foreign policy and the socio cultural settings. During the last 25 years, there has been drastic realization about health issues in the developing nations, which has given them hope of a better future for their children. Africa is one such region where poverty and hunger is widespread. This is the region where health care facilities are underdeveloped due to which many people face death. This paper, therefore, aims to devise and develop an essential health development policy, program and strategy for African region in order to eradicate the poverty. This forms the main thesis of the research paper (Mills, 1995). The role of health development has been gaining importance in the Africa and different countries are assisting the efforts by providing increased resources, which has put huge pressures on the weak health structure, organizational capabilities and workforce in one of the poorest regions of the country. There is a severe lack of planning and management of the health resources in this part of the world which has led to non- implementation of the health plans. The problem in the African region has been largely related to poverty, wars and conflicts, bad governance and non performance of health programs. This region also faces a huge virus of HIV and AIDS which increase the burden of disease (Loewenson, 1993). The domestic and international health polices for Africa have been drafted by international agreements of multiple countries which include Alma Ata Declaration of 1978, World Health Organization’s Bamako Initiative in 1987 and Paris Declaration of 2005, and including many more. The famous Alma Ata, known as the birth of primary health care or PHC, aims to provide a comprehensive and affordable health plan by providing health facilities at the most basic level. However the PHC failed to achieve its targets due to lack of infrastructure and facilities, staff, civil wars, natural disasters and issues of bad governance and corruption. Later various new international policies were tried which included the structural adjustment plan of the World Bank which was based on loans, privatization and cost recovery, however it failed to deliver due to various reasons (Sikosana, 2009). The Bamako Initiative was launched in 1987 which was aimed at access to quality health care and tackle the scarcity of medicine by a number of balanced policies which were implement able and are the perfect health development plan for the impoverished region of Africa. Together with the World Bank 1993 report, both the policies aim at providing the healthcare at the grass root level in order to eradicate poverty (Mills, 1995). The recommendations include improving primary healthcare at all the levels in an equitable manner which should be available to all the people at any income level. Another recommendation includes the decentralization of the management of the PHC to the district level as oppose to the earlier practice which limited the control to few big hospitals which was the reason for corruption and bad governance. The government should ensure equity of fees charged at all levels which would ensure homogeneity of services to rich and poor alike. The government should be highly committed to maintain and expand the PHC program and all the national health policies should be inline to one standard policy. The government should also closely monitor the whole policy implementation process and ensure services to the poor. Sustainable effort should also be made to for poverty alleviation through education, gender equity, improved mother and child health programs and AIDS control programs. For the African health problems, the policymakers should make integrated national plans and strengthen the health systems by empowerment, equity and sustainability of the efforts. The public private partnership is also essential for the sustainability of the strategy (Sikosana, 2009).

Enrollment System Essay

Enrollment is the focus of the Compfuturist that would lessen the institution’s difficulties in their Information System processing, solve data problems and an easier access of the establishment’s information. Every enrollment, 80-100 enrollees come for the dates of admission having a maximum of 30 for each level, in present time classrooms are consist of 15 students. An easier recording of files and a database to save documents will lessen the space being occupied by the records of the students. A faster transaction, easier ways for inputting datum and a convenient ways for saving files are offered for the use of the establishment by the enrolment system. The commonly used advertisements of schools are brochures, leaflets, banners and calling cards; the group also offers a website that will be used to improve its approach to people. The website would be a help for parents about the notice or updates of events and gatherings, it would also be a way to know the history of the institution and the contact details of the establishment. The incomplete requirements are the main problems during the enrollment, one of which is the student information, some of the information needed is not filled up and some are important to the school records. In the Pre-School it is required for them to have the copy of their birth certificate, two (2) copies of a 2Ãâ€"2 photo and an interview with the Pastor or Principal. For the grade-schoolers a photocopy of the birth certificate, the form 138, a certificate of Good Moral Character for transferee and an interview with the Pastor or Principal. Due to the uninformed people about the requirements needed some are not brought and are filed to be uncompleted forms. Each student has a folder that contains his or her information about the birth certificates, previous records from the earlier institution he or she attended, the quality point average for each year and also the permits signed by the parents. Enrollment takes time and effort from the parents, students and also from the teachers; every step of an enrolment, a teacher is assigned to instruct a parent or guardian what to do and where to go next. The slow process of enrolment makes the parents furious and makes the job even harder for the teachers for them to rush, that sometimes some records are not being filed or are not properly assigned. Missing documents are also a cause of problem for the institution, it might be placed to another folder or the parent forgot about it. A school’s updates about events and gatherings are the problems for teachers and parents. Students forget to tell their guardians or forgot to give the letter accustomed by their advisers. The result of the forgotten events cause students not to wear the proper attire, parents does not attend meetings and gatherings, students are thought to be absent for specific happenings and also parents become indignant about the unknown proceedings. Project Framework The Compfuturist Group offers the instituion. a system and a website that would shoulder the difficulties of the institution. The school appoints teachers to handle the student information during the enrollment. Software that is specially made only for Mabalacat Christian Academy and a website that would help the advertisement of the school increase. The system can only be open by an authorized member or the principal of the institution. Passwords and accounts would be made for the privacy policy made by the institution to safeguard each student’s information and background. The Student Information Sheet or Form would consist of the basic details about his or her family, previous schools the child attended, number of siblings, if there were awards he or she got from previous levels, address, contact number of the parent or guardian and more information that are to be filled by the guardian. An option will be given to the parent or guardian if the transaction of payment would be a full payment or a partial payment every quarter and a choice to have it paid through cash or cheque. A database would be given with a maximum capacity of 300 and a number of 50 students per level. A website would be provided for the institution that would only be used for the use of the school’s advertisement, featuring the facilities of the establishment, faculty members, and history of the school and updates of happenings. The page would be the source of parents to be updated to the school’s events; when, where and what to wear. Specific events require students to wear a garment requested by the institution for uniformity. The page can also be a source and guide for parents and guardians to know the details and history about the school. Contact details would be posted and an added detail of the page is that if parents are working abroad they could send the uncompleted requirement to the email of the school with attachment of the requirements. The Facebook page of the institution is also posted to the website and could be directed to the page created by the faculty members of the school. Statement of Objective Website and Enrollment System is a program extended to Mabalacat Christian Academy, a program that would make the transactions of requirements and documents, and also help about the school’s reputation about the improvement of its ways. It could solve the problems of the school since it started; the system only solves the problem of the school paperworks and will lessen the space of the documented files. The System is a program that would make the process of filing student information faster and easier to save for the school. The enrollment system’s purpose is to give a database for the files of students, a maximum of 300 files for the whole institution and an easier way of searching student files. A transaction that would make the access of information system easier for the authorized people, a faster accessibility in information provided and an improved process; the admission and acceptance of enrolees would be faster for the completion of forms would not be difficult for teachers to save and keep. The Website will inform the parents of the situations, cancellation of classes, school events, PTA meeting schedules, examination dates and payment dues. An account will be given to the principal or school head to access the student accounts and website if changes are to be made, the account given to the principal can also be used to check the number of students enrolled and to what level they are assigned to Importance of the Study The Compfuturist created a system only from Pre-School to Elementary levels and for an institution with one section per level, the system subjects only to the enrollment, saving and filing of documents and the postage of contact details of the institution. The use of the program is to lessen the burden of alphabetizing envelopes for each level and student, it also makes the search of a student file faster compared to the manual based of searching through metal drawers. A database that would show and save documents for specific purposes and privacy of files will be kept and safe from others to see. Only the Principal and the appointed faculty or member of the institution could access the information system of the database provided by the system. The institution would benefit from the free system that could be used for years and less updates of program would be given for the system is only for the use of Mabalacat Christian Academy. Parents and students would also benefit from it because information given from the old students will not be inputted again but be moved to the folder that consists of the level he or she is. The editing and adding of details is convenient even to those people who are not good in using computers. Less stressing and easier to use, is the way that the program or system offers to its benefactors. Radio buttons, scroll bars and more features of the program and website would be given to lessen the difficulty that some encounters in web pages and softwares. A free ten (10) months of maintenance is given for the institution and would make things better compared to the existing manual system.

History Why Did The Holocaust Happen - 1226 Words

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