Genetic Diseases

Gene Therapy
Team Members :

Tummala Pavan 21BT30030

Pulakurthi Vinuthna 21BT30021
Gunnu Hemanth 21BT30006
Thirupathi Yuvaraju 21BT10032
Addepalli Manjusri 21BT10001
Mathew Manoj 21BT30015
 Why focus on Genetic diseases and Gene therapy ?
- Many Genetic diseases often result from single Report taken from the official “WHO” website
genetic code errors.

- Current treatments for genetic diseases focus

on symptom management.

- Gene therapy holds promise for addressing a

wide range of genetic conditions,including color Report taken from ResearchGate.net and pubmed,
blindness, HIV, cancer etc. Published in Feb 2002
Some of the most common Genetic diseases and their Genetic therapy approaches :

Disease Inheritance Cause Gene Therapy Type of Mutation Symptoms

Pattern approach

Hemophilia A Autosomal Recessive F8 gene Mutation Replacement gene therapy Point mutations Prolonged bleeding, joint
pain

Cystitis Fibrosis X-linked CFTR gene Mutation CFTR modulator therapies Deletion, insertion, mutation Respiratory issues, digestive
problems

Duchenne Muscular Autosomal Dominant DMD gene Mutation Exon-skipping therapies Deletion, duplication, Muscle weakness, loss of
Dystrophy mutation ambulation

HUntington’s Disease Autosomal Recessive HTT gene Mutation Silencing or gene editing Expansion of CAG repeats Motor dysfunction, cognitive
decline

Sickle Cell Anemia Autosomal Recessive HBB gene Mutation CRISPR-based gene Point mutations in HBB Anemia, pain crises, organ
editing gene damage

Marfan Syndrome Autosomal Dominant FBN1 gene mutation Targeted therapies Various point mutations Connective tissue problems,
skeletal issues

Rett Syndrome X-linked MECP2 gene Symptomatic and Point mutations in MECP2 Loss of motor skills,
behavioral gene cognitive regression

Polycystic Kidney Autosomal Dominant PKD1 or PKD2 gene Supportive and Various point mutations Kidney cysts, hypertension,
Disease mutation symptomatic renal dysfunction
 Approaches To Gene Therapy
Gene Replacement Therapy
For monogenic diseases;
involves replacing a mutated
gene that causes disease with a
healthy gene
Gene Addition Gene Inhibition or Gene Editing
“Knockdown”
For complex and infectious diseases Making a targeted change to
Inactivating a mutated gene
introduces a new gene into the body the gene sequence
that is over-producing its
to help fight a disease,often to
product by targeting RNA
supplement a targeted therapeutic
agent

➢ The aim of Gene Replacement Therapy (GRT) is to provide sufficient gene expression in enough targeted cells to ameliorate or
correct dysfunctional phenotype
Suitable for: Recessive disorders, single gene mutations, and X- Implementation
linked diseases ● Either directly in vivo or through ex
Generally unsuitable for: vivo cell therapy
Dominant disorders where an errant gene codes for destructive or ● Vehicle/vector used to deliver
interfering proteins therapeutic transgene
 Practical Gene therapy approaches
❏ Germline therapy Practically this method is used to treat the
❏ Somatic gene therapy genetic disease causing variations of genes
❏ Gene therapy for cancer which are passed from their parents to their
❏ Pro drug gene therapy children. The process involves introducing a
healthy DNA into the reproductive cells ie,
sperms or eggs
➢ Gene therapy in people have shown success in treating
certain diseases .
➢ ex: immune deficiency, hemophilia, leukemia etc
➢ Used to treat Parkinson's disease (loosing of brain cells
due to dopamine(signaling molecule) deficiency), cured
by introducing 3 genes that give the cells the ability to
make dopamine
The first gene therapy was done in 2017 for a gene(RPE65) that
causes vision loss. In 2018 the market of companies developing gene
therapies is at US$1Billion, and by 2027 the gene therapy market is
expected to reach a revenue of US 6$Billion to $19Billion.

Watson and crick discovered the structure of DNA in 1953, by 2053

there might be a gene based therapy for every disease (cancer, heart
disease etc) .
There is a need for more sophisticated and diverse gene therapy approaches
at low cost with near zero errors
Genetic delivery and Delivering a gene and improper to the wrong tissue would be
Activation inefficient, and it could cause health problems for the patient.

Gene-delivery vectors must be able to avoid the body's natural

surveillance system. An unwelcome immune response could
cause serious illness or even death.One way researchers avoid
Immune response triggering an immune response is by delivering viruses to cells
outside of the patient's body. Another is to give patients drugs
to temporarily suppress the immune system during treatment.
Challenges
of Gene Ideally, an introduced gene will continue working for the rest of
the patient's life. For this to happen, the introduced gene must
Therapy Disrupting Important become a permanent part of the target cell's genome, usually
genes in target cells by integrating, or "stitching" itself, into the cell's own DNA,there
are high chances it disrupts.

Developing a new therapy,including taking it through the clinical

trials necessary for government approval, is very expensive.With
Commercial Viability a limited number of patients to recover those expenses from,
developers may never earn money from treating such rare
disorders.And some patients may never be able to afford them.
Thank you !