Gene therapy and gene editing techniques show promise for treating genetic diseases. CRISPR-Cas9 allows geneticists to precisely edit DNA sequences by removing, adding, or altering sections of the genome. While few treatments currently exist, gene therapy aims to insert new genes or replace defective ones to treat underlying genetic mutations. Researchers believe genetic therapies will become standard of care for many rare genetic diseases by 2036. However, gene therapy also carries risks like immune reactions, off-target effects, and possible tumor formation that researchers continue working to address through alternative vectors like stem cells or liposomes.

1. The treatment of genetic
disease
Dr. dr. Mitayani, M. Si. Med.

2. LEARNING OBJECTIVES
Student should be able to understand:
• The current state of the treatment of genetic disease
• Special considerations in treating genetic disease
• Treatment by the manipulation of metabolism
• Treatment to increase the function of the affected gene or protein
• Gene therapy

3. The current state of the treatment of genetic
disease
• In a study involving 1,430 researchers with good knowledge in the
treatment of rare genetic diseases  most of respondents believed
that genetic therapies would be the standard of care for rare genetic
diseases before 2036.
• Gene editing techniques using nuclease enzyme: CRISPR-Cas9,
transcription activator-like effector nucleases (TALENs), Zinc-finger
nucleases (ZFNs)

4. What is CRISPR-Cas9?
• Clustered regularly interspaced short palindromic repeats (CRISPR)-
associated nuclease enzyme Cas9 (Cas9)
• is a unique technology that enables geneticists and medical
researchers to edit parts of the genome by removing, adding or
altering sections of the DNA sequence.
• consists of two key molecules that introduce a change (mutation) into
the DNA:
a. Cas9 enzyme  DNA scissors
b. guide RNA (gRNA)  guide for Cas9 enzyme

5. Special considerations in treating genetic
disease
• Although few treatments are available for these severe genetic
conditions, health professionals can often provide supportive care,
such as pain relief or mechanical breathing assistance, to the affected
individual.
• Most treatment strategies for genetic disorders do not alter the
underlying genetic mutation; however, a few disorders have been
treated with gene therapy.

6. Treatment by the manipulation of metabolism
• Inborn error metabolism is a group of genetic conditions, which result
from genetic changes that disrupt the production of specific enzymes.
• Example: Phenylketonuria
• Can be treated by enzyme replacement therapy or dietary changes.

7. GENE THERAPY
• Sometimes the whole or part of a gene is defective or missing from
birth. This is typically referred to as a genetically inherited mutation.
• In addition, healthy genes can change (mutate) over the course of our
lives. These acquired mutations can be caused by environmental
exposures. The good news is that most of these genetic changes
(mutations) do not cause disease.
• But some inherited and acquired mutations can cause developmental
disorders, neurological diseases, and cancer.

8. Gene
therapy
add genes
to the
body
replace a
gene
Turn off
the
mutated
gene

9. GENE THERAPY
• To insert new genes directly into cells, scientists use a vehicle called a
“vector.” Vectors are genetically engineered to deliver the necessary
genes for treating the disease.
• Vectors need to be able to efficiently deliver genetic material into
cells, and there are different kinds of vectors.
• Viruses are currently the most commonly used vectors in gene
therapies because they have a natural ability to deliver genetic
material into cells.
• Before a virus can be used to carry therapeutic genes into human
cells, it is modified to remove its ability to cause infectious disease.

10. GENE THERAPY
• Gene therapy can be used to modify cells inside or outside the
body. When a gene therapy is used to modify cells inside the body, a
doctor will inject the vector carrying the gene directly into the
patient.
• When gene therapy is used to modify cells outside the body, doctors
take blood, bone marrow, or another tissue, and separate out specific
cell types in the lab.
• The vector containing the desired gene is introduced into these cells.
The cells are later injected into the patient, where the new gene is
used to produce the desired effect.

13. Gene therapy was first used to treat
genetic disease, especially
monogenic.
Efforts were then made to treat
cancer.

14. GENE THERAPY
• Risk of Gene therapy: unwanted immune system reaction due to
viruses as the vectors, targeting the wrong cells because viruses can
affect more than one type of cells, infection caused by the virus, and
the possibility of causing a tumor.
• Solutions: some clinical trials are trying to use stem cells or liposomes
as the new vectors.

15. TUGAS INDIVIDU
• Tambahkan mengenai treatment untuk penyakit genetik yang
mahasiswa kerjakan pada kuliah sebelumnya.
• Treatment dimaksud adalah treatment secara genetik, bukan klinis
(antipiretik, antibiotik, dll.)

16. THANK YOU