Gene therapy involves introducing genetic material into a patient's cells to treat a disease. The first successful human gene therapy trial took place in 1990 to treat ADA-SCID. Since then over 2,300 clinical trials have been conducted, mostly in phase I. There are two main types - somatic cell gene therapy, which affects only the individual, and germline gene therapy, which can be inherited. Recent breakthroughs include FDA-approved CAR-T therapies to treat some cancers, and experimental gene therapy curing sickle cell disease in one patient. However, gene therapy also faces challenges in terms of costs, safety, and ethical and regulatory issues.

1. Gene therapy

2. Introduction
 In medicine, gene therapy (also called human gene
transfer) is the therapeutic delivery of nucleic acid into a
patient's cells as a drug to treat disease.[ The first attempt at
modifying human DNA was performed in 1980 by Martin
Cline, but the first successful nuclear gene transfer in
humans, approved by the National Institutes of Health, was
performed in May 1989.[2] The first therapeutic use of gene
transfer as well as the first direct insertion of human DNA into
the nuclear genome was performed by French Anderson in a
trial starting in September 1990.
 Between 1989 and February 2016, over 2,300 clinical trials
had been conducted, more than half of them in phase I.

4. Background
 Gene therapy was conceptualized in 1972, by authors who urged
caution before commencing human gene therapy studies.
 After extensive research on animals throughout the 1980s and a
1989 bacterial gene tagging trial on humans, the first gene
therapy widely accepted as a success was demonstrated in a
trial that started on 14 September 1990, when Ashi DeSilva was
treated for ADA-SCID.

5. Somatic Germline
Cell types
 In somatic cell gene therapy
(SCGT), the therapeutic genes
are transferred into any cell
other than a gamete, germ
cell, gametocyte, or
undifferentiated stem cell. Any
such modifications affect the
individual patient only, and are
not inherited by offspring.
Somatic gene therapy
represents mainstream basic
and clinical research, in which
therapeutic DNA (either
integrated in the genome or as
an external episome or plasmid)
is used to treat disease.
 In germline gene therapy (GGT), germ
cells (sperm or egg cells) are modified
by the introduction of functional genes
into their genomes. Modifying a germ
cell causes all the organism's cells to
contain the modified gene. The change
is therefore heritable and passed on to
later generations. Australia, Canada,
Germany, Israel, Switzerland, and the
Netherlands prohibit GGT for
application in human beings, for
technical and ethical reasons, including
insufficient knowledge about possible
risks to future generations and higher
risks versus SCGT. The US has no
federal controls specifically addressing
human genetic modification (beyond
FDA regulations for therapies in
general).

6. Speculative uses
Fertility- Gene Therapy
techniques have the potential
to provide alternative
treatments for those with
infertility. Recently,
successful experimentation
on mice has proven that
fertility can be restored by
using the gene therapy
method,
CRISPR. Spermatogenical
stem cells from another
organism were transplanted
into the testes of an infertile
male mouse. The stem cells
re-established
spermatogenesis and fertility.

7. How does gene therapy work?
 A gene that is inserted directly
into a cell usually does not
function. Instead, a carrier
called a vector is genetically
engineered to deliver the gene.
Certain viruses are often used
as vectors because they can
deliver the new gene by
infecting the cell. The viruses
are modified so they can't
cause disease when used in
people. Some types of virus,
such as retroviruses, integrate
their genetic material (including
the new gene) into a
chromosome in the human cell.
Other viruses, such as
adenoviruses, introduce their
DNA into the nucleus of the cell,
but the DNA is not integrated
into a chromosome

8. 2017 Was the Year of Gene-
Therapy Breakthroughs
 Decades in the making, gene
therapy—the idea of modifying
a person’s DNA to treat
disease—represents a major
shift in medicine. Instead of
just treating symptoms like the
vast majority of drugs on the
market, gene therapy aims to
correct the underlying genetic
cause of a disease. Doctors
and scientists hope these
treatments will be a one-shot
cure.
 Last year, we wrote that 2016
was gene therapy’s most
promising year. But 2017
proved to be even bigger.

9. Cancer killers
 This year the FDA approved two pioneering
treatments, Kymriah and Yescarta, that use a patient’s own
immune cells to fight rare types of cancer. Called CAR-T
therapies, these “living drugs” are made by extracting T cells
from patients and genetically engineering them to go after
and destroy cancer cells. The cells are then infused back into
the body. So far, these therapies are being tested only in a
handful of lethal cancers as a last resort when more
traditional treatments, like chemotherapy, don’t work.
Kymriah treats a bone marrow cancer that affects children
and young adults, and Yescarta treats a type of lymphoma.
Some patients have had remarkable recoveries and remain
in remission months or years later.

10. Sickle-cell cure
 Researchers announced that a
teenage boy in France had
been cured of sickle-cell
disease after receiving an
experimental gene therapy
developed by Bluebird Bio.
Caused by a single genetic
mutation, sickle-cell is an
inherited blood disorder that
affects 100,000 people in the
U.S. and millions around the
world. Scientists removed stem
cells from the boy’s bone
marrow and modified them in
the lab by introducing copies of
a gene to prevent his red blood
cells from becoming “sickled.”
When the treated cells were
infused back into his body, they
began to make normal blood
cells.

11. Speculative uses
Gene doping- Athletes
might adopt gene therapy
technologies to improve their
performance. Gene doping is
not known to occur, but
multiple gene therapies may
have such effects. Kayser et
al. argue that gene doping
could level the playing field if
all athletes receive equal
access. Critics claim that any
therapeutic intervention for
non-
therapeutic/enhancement
purposes compromises the
ethical foundations of
medicine and sports.

12. Human genetic engineering
 Genetic engineering could be used to cure diseases, but also
to change physical appearance, metabolism, and
even improve physical capabilities and mental faculties such
as memory and intelligence. Ethical claims about germline
engineering include beliefs that every foetus has a right to
remain genetically unmodified, that parents hold the right to
genetically modify their offspring, and that every child has the
right to be born free of preventable diseases.] For parents,
genetic engineering could be seen as another child
enhancement technique to add to diet, exercise, education,
training, cosmetics, and plastic surgery. Another theorist
claims that moral concerns limit but do not prohibit germline
engineering

13. The cost of gene therapy
 Many genetic disorders that can be targeted with gene
therapy are extremely rare.
 Gene therapy therefore often requires an individual, case-by-
case approach. This may be effective, but may also be very
expensive.
 Making sure the new gene doesn’t disrupt the function of
other genes
 ideally, a new gene introduced by gene therapy will integrate
itself into the genome of the patient and continue working for the
rest of their lives.
 There is a risk that the new gene will insert itself into the path of
another gene, disrupting its activity.

14. Regulations
 Regulations covering genetic modification are part of general
guidelines about human-involved biomedical research. There
are no international treaties which are legally binding in this
area, but there are recommendations for national laws from
various bodies.
 The Helsinki Declaration (Ethical Principles for Medical
Research Involving Human Subjects) was amended by
the World Medical Association's General Assembly in 2008. This
document provides principles physicians and researchers must
consider when involving humans as research subjects. The
Statement on Gene Therapy Research initiated by the Human
Genome Organization (HUGO) in 2001 provides a legal
baseline for all countries. HUGO’s document emphasizes
human freedom and adherence to human rights, and offers
recommendations for somatic gene therapy, including the
importance of recognizing public concerns about such research