GENE GENE THERAPYTHERAPY

What Genes can doWhat Genes can do

Genes, which are carried on Genes, which are carried on chromosomes, are the basic physical chromosomes, are the basic physical and functional units of heredity. and functional units of heredity. Genes are specific sequences of Genes are specific sequences of bases that encode instructions on bases that encode instructions on how to make proteins. it’s the how to make proteins. it’s the proteins that perform most life proteins that perform most life functions and even make up the functions and even make up the majority of cellular structures.majority of cellular structures.

Why Genetic DisordersWhy Genetic Disorders

When genes are When genes are altered so that the altered so that the encoded proteins encoded proteins are unable to carry are unable to carry out their normal out their normal functions, genetic functions, genetic disorders can disorders can resultresult. .

All of us carry some defective Genes, All of us carry some defective Genes, some are apparent and many in apparentsome are apparent and many in apparent

Each of us carries about half a dozen defective Each of us carries about half a dozen defective genes. We remain blissfully unaware of this fact genes. We remain blissfully unaware of this fact unless we, or one of our close relatives, are unless we, or one of our close relatives, are amongst the many millions who suffer from a amongst the many millions who suffer from a genetic disease. About one in ten people has, or genetic disease. About one in ten people has, or will develop at some later stage, an inherited will develop at some later stage, an inherited genetic disorder, and approximately 2,800 genetic disorder, and approximately 2,800 specific conditions are known to be caused by specific conditions are known to be caused by defects (mutations) in just one of the patient's defects (mutations) in just one of the patient's genes. genes.

We Inherit from ParentsWe Inherit from Parents

Most of us do not suffer any harmful effects Most of us do not suffer any harmful effects from our defective genes because we carry two from our defective genes because we carry two copies of nearly all genes, one derived from our copies of nearly all genes, one derived from our mother and the other from our father. The only mother and the other from our father. The only exceptions to this rule are the genes found on exceptions to this rule are the genes found on the male sex chromosomes. Males have one X the male sex chromosomes. Males have one X and one Y chromosome, the former from the and one Y chromosome, the former from the mother and the latter from the father, so each mother and the latter from the father, so each cell has only one copy of the genes on these cell has only one copy of the genes on these chromosomes chromosomes

Law of InheritanceLaw of Inheritance

In the majority of cases, one normal gene In the majority of cases, one normal gene is sufficient to avoid all the symptoms of is sufficient to avoid all the symptoms of disease. If the potentially harmful gene is disease. If the potentially harmful gene is recessive, then its normal counterpart will recessive, then its normal counterpart will carry out all the tasks assigned to both. carry out all the tasks assigned to both. Only if we inherit from our parents two Only if we inherit from our parents two copies of the same recessive gene will a copies of the same recessive gene will a disease develop. disease develop.

What is Gene TherapyWhat is Gene Therapy

Gene therapyGene therapy is the insertion of genes is the insertion of genes into an individual's cells and tissues to into an individual's cells and tissues to treat a disease, such as a hereditary treat a disease, such as a hereditary disease in which a deleterious mutant disease in which a deleterious mutant allele is replaced with a functional one. allele is replaced with a functional one. Although the technology is still in its Although the technology is still in its infancy, it has been used with some infancy, it has been used with some success. success.

How It WorksHow It Works

A vector delivers the therapeutic gene into A vector delivers the therapeutic gene into a patient’s target cella patient’s target cell

The target cells become infected with the The target cells become infected with the viral vectorviral vector

The vector’s genetic material is inserted The vector’s genetic material is inserted into the target cellinto the target cell

Functional proteins are created from the Functional proteins are created from the therapeutic gene causing the cell to return therapeutic gene causing the cell to return to a normal stateto a normal state

Gene Therapy is ExperimentalGene Therapy is Experimental

Advances in understanding and Advances in understanding and manipulating genes have set the stage for manipulating genes have set the stage for scientists to alter a person's genetic scientists to alter a person's genetic material to fight or prevent disease. Gene material to fight or prevent disease. Gene therapy is an experimental treatment that therapy is an experimental treatment that involves introducing genetic material involves introducing genetic material (DNA or RNA) into a person's cells to fight (DNA or RNA) into a person's cells to fight disease. disease.

Majority are TrialsMajority are Trials

Gene therapy is Gene therapy is being studied in being studied in clinical trials clinical trials (research studies (research studies with people) for many with people) for many different types of different types of cancer and for other and for other diseases. It is not diseases. It is not currently available currently available outside a clinical outside a clinical trials trials

What Gene therapy can AchieveWhat Gene therapy can Achieve

Replacing a mutated Replacing a mutated gene that causes gene that causes disease with a healthy disease with a healthy copy of the gene.copy of the gene.

Inactivating, or “knocking Inactivating, or “knocking out,” a mutated gene that out,” a mutated gene that is functioning improperly.is functioning improperly.

Introducing a new gene Introducing a new gene into the body to help fight into the body to help fight a disease.a disease.

Uses of gene therapyUses of gene therapy Replace missing or defective genes; Replace missing or defective genes;

Deliver genes that speed the destruction of cancer Deliver genes that speed the destruction of cancer cells; cells;

Supply genes that cause cancer cells to revert back Supply genes that cause cancer cells to revert back to normal cells; to normal cells;

Deliver bacterial or viral genes as a form of Deliver bacterial or viral genes as a form of vaccination; vaccination;

Provide genes that promote or impede the growth of Provide genes that promote or impede the growth of new tissue; and; new tissue; and;

Deliver genes that stimulate the healing of damaged Deliver genes that stimulate the healing of damaged tissue. tissue.

Genes are MedicineGenes are Medicine ??

Gene therapy is ‘the use of genes as Gene therapy is ‘the use of genes as medicine’. It involves the transfer of a medicine’. It involves the transfer of a therapeutic or working gene copy into therapeutic or working gene copy into specific cells of an individual in order to specific cells of an individual in order to repair a faulty gene copy. Thus it maybe repair a faulty gene copy. Thus it maybe used to replace a faulty gene, or to used to replace a faulty gene, or to introduce a new gene whose function is to introduce a new gene whose function is to cure or to favourably modify the clinical cure or to favourably modify the clinical course of a condition.course of a condition.

Goal of Gene therapyGoal of Gene therapy A normal gene may be inserted into a non-specific A normal gene may be inserted into a non-specific

location within the genome to replace a non-functional location within the genome to replace a non-functional gene. This approach is most common.gene. This approach is most common.

An abnormal gene could be swapped for a normal gene An abnormal gene could be swapped for a normal gene through homologous recombination.through homologous recombination.

The abnormal gene could be repaired through selective The abnormal gene could be repaired through selective reverse mutation, which returns the gene to its normal reverse mutation, which returns the gene to its normal function.function.

The regulation (the degree to which a gene is turned on or The regulation (the degree to which a gene is turned on or off) of a particular gene could be altered.off) of a particular gene could be altered.

Delivering desired GenesDelivering desired Genes

Gene Therapy CorrectsGene Therapy Corrects

Gene therapy is a Gene therapy is a technique for technique for correcting defective correcting defective genes responsible for genes responsible for disease disease development. development. Researchers may Researchers may use one of several use one of several approaches for approaches for correcting faulty correcting faulty genes: genes:

First Approved Gene TherapyFirst Approved Gene Therapy

On September 14, 1990 at the U.S. On September 14, 1990 at the U.S. National Institutes of Health, W. French National Institutes of Health, W. French Anderson M.D. and his colleagues R. Anderson M.D. and his colleagues R. Michael Blaese, M.D., C. Bouzaid, M.D., Michael Blaese, M.D., C. Bouzaid, M.D., and Kenneth Culver, M.D., performed the and Kenneth Culver, M.D., performed the first approved gene therapy procedure on first approved gene therapy procedure on four-year old Ashanthi DeSilva. Born with four-year old Ashanthi DeSilva. Born with a rare genetic disease called severe a rare genetic disease called severe combined immunodeficiency (SCID), combined immunodeficiency (SCID),

What did they doWhat did they do

In Ashanthi's gene In Ashanthi's gene therapy procedure, therapy procedure, doctors removed white doctors removed white blood cells from the blood cells from the child's body, let the cells child's body, let the cells grow in the laboratory, grow in the laboratory, inserted the missing inserted the missing gene into the cells, and gene into the cells, and then infused the then infused the genetically modified genetically modified blood cells back into the blood cells back into the patient's bloodstream.patient's bloodstream.

A success storyA success story

As of early 2007, she was still in good As of early 2007, she was still in good health, and she was attending college. health, and she was attending college. Some would state that the study is of Some would state that the study is of great importance despite its indefinite great importance despite its indefinite results, if only because it demonstrated results, if only because it demonstrated that gene therapy could be practically that gene therapy could be practically attempted without adverse consequences.attempted without adverse consequences.

SafetySafety

Safety: Although Safety: Although viral vectors are viral vectors are occasionally occasionally created from created from pathogenic viruses, pathogenic viruses, they are modified in they are modified in such a way as to such a way as to minimize the risk of minimize the risk of handling them.handling them.

What are the ethical issues What are the ethical issues surrounding gene therapy?surrounding gene therapy?

How can “good” and “bad” uses of gene therapy be How can “good” and “bad” uses of gene therapy be distinguished?distinguished?

Who decides which traits are normal and which constitute Who decides which traits are normal and which constitute a disability or disorder?a disability or disorder?

Will the high costs of gene therapy make it available only Will the high costs of gene therapy make it available only to the wealthy?to the wealthy?

Could the widespread use of gene therapy make society Could the widespread use of gene therapy make society less accepting of people who are different?less accepting of people who are different?

Should people be allowed to use gene therapy to Should people be allowed to use gene therapy to enhance basic human traits such as height, intelligence, enhance basic human traits such as height, intelligence, or athletic ability?or athletic ability?

The Future of Gene TherapyThe Future of Gene Therapy

Current uses of gene therapy focus on Current uses of gene therapy focus on treating or curing existing conditions. In treating or curing existing conditions. In the future, the focus could shift to the future, the focus could shift to prevention. As more of the human prevention. As more of the human genome is understood, medicine will know genome is understood, medicine will know more about which genes contribute to or more about which genes contribute to or cause disease. With that knowledge in cause disease. With that knowledge in hand, gene therapy could be used to head hand, gene therapy could be used to head off problems before they occur. off problems before they occur.

Are we Distorting the Nature?Are we Distorting the Nature?

Do not forget Genes can be Do not forget Genes can be Unpredictable ?Unpredictable ?