“Science that deals with ways to diagnose and treat diseases by understanding the way genes, proteins, and other cellular molecules work”

1. Molecular medicine
“Unlocking your genetic secrets”

2. Molecular medicine
“Science that deals with ways to diagnose and treat diseases by understanding the way genes,
proteins, and other cellular molecules work”
Diagnosis
Treatment
Molecular tools &
Techniques

3. • Body temperature is a biomarker for fever while your blood glucose level is a marker for diabetes.
• Today, biomarkers can be measured down to a molecule. These types of signals have increased in
their importance to medical diagnosis and prognosis.
• The work promises to reshape how doctors diagnose and treat disease and how pharmaceutical
companies pursue drug development.

4. Currently, molecular medicine encompass
• Elucidation of the genetic basis of disease
• Diagnosis of the disease
• Design of an appropriate approach to disease management or therapy
• In order to develop a therapeutic molecule against any disease, it is very essential to understand the precise mechanism of
the disease and the specific target that is associated with it.
• Enhancement of knowledge in the field of biotechnology, molecular biology and medicinal chemistry improved the basic
understanding of disease mechanism, mechanism of drug action and hence a paradigm shift in drug discovery approach
towards development of targeted drug discovery.

5. Biomarkers in molecular medicine
• Biomarkers include genes and genetic variations, differences in messenger RNA (mRNA) and/or protein expression,
posttranslational modifications of proteins, and metabolite levels.
• Biomarker testing is a way to look for genes, proteins, and other substances (called biomarkers) that can provide information
about a disease condition.
• There is increasing interest and enthusiasm in molecular markers as tools for cancer detection and prognosis, as they are
noninvasive and detect cancers in their early stages of development.
• In cancer research, molecular biomarkers refer to substances that are indicative of the presence of cancer in the body.
• There is tremendous variety of biomarkers, which can include proteins (e.g., an enzyme or receptor), nucleic acids (e.g., a
microRNA or other non-coding RNA), antibodies, and peptides,

6. • The FDA approved the drugs target solid tumors that show specific biomarkers—namely microsatellite instability (MSI)(genome-wide
alterations in repetitive DNA sequences seen in hereditary nonpolyposis colorectal cancer (HNPCC) and neurotrophic receptor tyrosine
kinase (NTRK) gene fusion (Rearrangements in the NTRK genes can result in two genes fusing together and producing altered TRK proteins,
which can lead to uncontrolled growth of cancer cells)—irrespective of where the tumors are growing in the body.
(For a field that has been anchored to anatomy in the diagnosis of disease, a biomarker-first approach represents a sea change)
• Beyond cancer, researchers are investigating a pro-peptide (Protein precursor) known as PRO-C3 as a potential biomarker for non-alcoholic
steatohepatitis (NASH) , which currently requires an invasive liver biopsy for diagnosis, as well as autoantibodies viz., anti-citrullinated
protein antibodies (ACPA) that could help diagnosis of rheumatoid arthritis before joint damage occurs.

7. DNA tests can predict the diseases you may face.
• Inherited diseases led by mutations in a gene.
• The genes are located on chromosomes and transmit to the off-springs. Thus, a mutation that occurred in a gene is also inherited
to the consecutive generations, results in genetic abnormalities.
• There is a long list of inherited disorders where molecular techniques such as PCR has a significant role to play. A typical
example is β-thalassaemia (Thalassemia is an inherited blood disorder wherein the body produces an inadequate amount of
haemoglobin.).
• Beta thalassemia is caused by changes (mutations) in the HBB gene while alpha thalassemia is caused by mutations in the HBA1
and/or HBA2 genes.
Inherited disorders Affected gene
Adenosine deaminase deficiency ada (involved in purine metabolism)
Cystic fibrosis cftr gene
Taysach’s disease hexA (Hexosaminidase A)
Sickle cell anemia Beta-globin gene
Retinoblastoma Rb gene product
PhenylKetonuria Phenylalanine Hydroxylase
Hemophilia A Factor VIII
Hemophilia B Factor IX

8. Therapeutics targeting DNA:
• Drugs targeting DNA are either DNA intercalators (proflavin), minor groove binders (Distamycin A,
Netropsin), alkylating agents (Benzopyrene) or nucleotide analogs (Cytabine, Gemcitibine). These drugs act
by altering/regulating the replication/transcription or induce apoptosis.
• In addition to these rapid progress has been accomplished in last two decades in development of nucleic acid
based therapeutic systems such as gene therapy and DNA vaccines.
• DNA vaccination promises great potential for fighting a variety of diseases.
• DNA can be introduced by viral or bacterial vectors or through uptake of 'naked' or complexed DNA.
• The use of polymeric materials to elicit delivery holds promise as PLGA, chitosan and PEI has shown
potential results in pre-clinical and clinical studies.

9. Therapeutics targeting RNA:
• RNA therapy is a promising therapeutics for the treatment of so called untreatable diseases such as cancer, viral infections, genetic and metabolic disorders.
• Anisense RNA, small interfering RNA (Si RNA) and micro RNA (miRNA) has been tested extensively for diverse therapeutic application and its efficacy
has been well demonstrated in vitro.
• A growing number of reports have shown that aberrant miRNA expression is a common feature of human diseases including cancer, which has sparked
interest in targeting these regulators of gene expression as a means of ameliorating these diseases.
• Currently there are 132 RNA/Oligonucleotide based products for ten therapeutic areas, which are in the different stages of development from preclinical to
Phase III clinical trials.
• Interfering RNA can be used for the treatment of cancer, viral diseases (HIV, CMV, Influenza), genetic and metabolic disorders

10. Drugs targeting proteins:
• Most common protein targets for which successful drugs have been developed include proteases, kinases, G Protein Coupled
Receptors (GPCRs) and nuclear hormone receptors.
• GPCRs (23%) and enzymes (50%) represent the most important target classes of proteins for drug discovery.
• Complexity in development of drugs targeting proteins are cross reactivity, toxicity and development of drug resistance. This is
more pronounced in synthetic molecules, whereas the problem is comparatively less in molecules obtained from natural sources for
instance molecules from ethanobotanical source.

11. Gene therapy
• Techniques for correcting defective genes responsible for disease development.
• Gene therapy is essentially a technique in which scientists utilize genes in order to treat or prevent disease.
• Designed to introduce genetic material into cells to compensate for abnormal genes to make beneficial protein
• If a mutated gene causes a necessary protein to be faulty or missing, gene therapy may be able to introduce a normal copy
of the gene to restore the function of the protein.
• A number of human inherited disorders have been corrected in cultured cells and several diseases (e.g. malignant
melanoma and severe combined immunodeficiency disease, SCID) are currently being treated by gene therapy techniques
indicating that gene therapy is likely to be a powerful therapeutic technique against a host of diseases in coming years
• Some of the different types of viruses used as gene therapy vectors: Retroviruses, Adenoviruses , Adeno-associated viruses
, Herpes simplex viruses

12. DNA vaccines
• DNA vaccination is a technique for protecting an animal against disease by injecting it with genetically
engineered DNA so cells directly produce an antigen, resulting in a protective immunological response.
• The two most popular approaches were in 1999 injection of DNA in saline: by using a standard hypodermic
needle; or by using a gene gun delivery.
• India may be first country to develop DNA vaccine for Covid-19. DNA-based COVID-19 vaccine ZyCoV-D
developed by pharma major, Zydus Cadila and currently undergoing clinical trials.
• This approach offers several potential advantages over traditional approaches, including the stimulation of
both B-and T-cell responses, improved vaccine stability, the absence of any infectious agent and the
relative ease of large-scale manufacture.’
• These vaccines take a small portion of the virus' own genetic information – enough to trigger an immune
response – inject them into cells which then produce the spike proteins to be recognised by the immune
system.
• DNA vaccines are believed to be more stable than their RNA counterparts owing to the presence of a
substance called thymine.
• mRNA Covid-19 Vaccine (Pfizer/BioNTech) - BNT162b2