Nucleic acids are biopolymers that are essential for life. They include DNA and RNA and are composed of nucleotides. DNA stores and transmits genetic information through replication and plays roles in gene expression and regulation. Issues with gene therapy include short-lived effects, immune responses, and difficulties targeting multi-gene disorders. A new "Trojan horse" technique uses DNA origami to encapsulate chemotherapy drugs and deliver them inside drug-resistant cancer cells without detection to kill the cells.
These slides may be helpful for grabbing basic knowledge regarding Nucleic acids for the students of Microbiology, Biochemistry, Nursing, Agriculture, Veterinary,Pharmacy..etc
These slides may be helpful for grabbing basic knowledge regarding Nucleic acids for the students of Microbiology, Biochemistry, Nursing, Agriculture, Veterinary,Pharmacy..etc
A mutation is a change that occurs in our DNA sequence, either due to mistakes when DNA is copied or as the result of environmental factors such as UV light. The DNA sequence of a gene can be altered in a number of ways. Gene mutations have varying effects on health, depending on where they occur and whether they alter the function of essential proteins. Mutations are two types that are Gene mutation and Chromosome mutation. Gene mutation are further divided into Point and frameshift mutation. Point mutation are three types ie. Silent mutation, Missense mutation and Nonsense mutation. Frameshift mutation are of two types that are addition and deletion. Chromosome mutations are further classified into Deletion, duplication, inversion and translocation.
This ppt covers:
Central dogma, discoverer of central dogma, Reason why its called central dogma, DNA, RNA, Protein, functions of protein, Types of RNA, DNA replication, Protein synthesis, Transcription, Translation, Exceptions of central dogma, Reverse transcription , prions, genetic code, mutation with types and causes
A mutation is a change that occurs in our DNA sequence, either due to mistakes when DNA is copied or as the result of environmental factors such as UV light. The DNA sequence of a gene can be altered in a number of ways. Gene mutations have varying effects on health, depending on where they occur and whether they alter the function of essential proteins. Mutations are two types that are Gene mutation and Chromosome mutation. Gene mutation are further divided into Point and frameshift mutation. Point mutation are three types ie. Silent mutation, Missense mutation and Nonsense mutation. Frameshift mutation are of two types that are addition and deletion. Chromosome mutations are further classified into Deletion, duplication, inversion and translocation.
This ppt covers:
Central dogma, discoverer of central dogma, Reason why its called central dogma, DNA, RNA, Protein, functions of protein, Types of RNA, DNA replication, Protein synthesis, Transcription, Translation, Exceptions of central dogma, Reverse transcription , prions, genetic code, mutation with types and causes
Cellular defense against fatal associations between proteins
and DNA
Date:
July 3, 2014
DNA 'replication fork' reconstituted for the first time
Date:
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3. Definition
Biopolymers/large biomolecules.
Essential for life.
Includes DNA and RNA
Made from monomers.
Known As nucleotides.
Named because ,
First found in the nucleus of cells,
Later on discovered outside the nucleus.
4. History of Nucleic acid
• In 1869, Friedrich Miescher
Isolated intact nuclei from cells & analyzing chemical content.
Extracted substances rich in “P” and “N”.
Which was known as "nucleic acids."
• In 1944, Avery, MacLeod and McCarty
Expressed it as DNA & found as the genetic material.
By using bacterial DNA to transform the genetic material of
other bacteria.
5. Composition of Nucleic Acids
Linears polymers of nucleotides.
Each nucleotide consists of 3 components:
Purine or pyrimidine nucleobase (nitrogenous base)
Pentose sugar
Phosphate group
6. Composition of Nucleic Acids
A nucleic acid polymer, polynucleotide,forms from the nucleotide
monomers when the phosphate of one nucleotide bonds to the
sugar of the next nucleotide.
Resulting a repeating sugar-phosphate backbone with protruding
nitrogenous bases.
9. DNA Replication
3 main features of the DNA synthesis reaction:
i. DNA polymerase-I catalyzes formation of phosphodiester bond
between 3’-OH of the deoxyribose (on the last nucleotide) and
the 5’-phosphate of the dNTP.
• Energy for this reaction is derived from the release of two of the
three phosphates of the dNTP.
ii. DNA polymerase “finds” the correct complementary dNTP at each
step in the lengthening process.
• rate ≤ 800 dNTPs/second & low error rate.
iii. Direction of synthesis is 5’ to 3’
12. Initiation of replication
Segments of single-stranded DNA are called template strands.
Gyrase (a type of topoisomerase) relaxes the supercoiled DNA.
Initiator proteins and DNA helicase binds to the DNA at the
replication fork and untwist the DNA using energy derived from
ATP.(Hydrolysis of ATP causes a shape change in DNA helicase)
DNA primase next binds to helicase producing a complex called a
primosome (primase is required for synthesis),
13. Initiation of replication
Primase synthesizes a short RNA primer of 10-12 nucleotides,
to which DNA polymerase III adds nucleotides.
Polymerase III adds nucleotides 5’ to 3’ on both strands
beginning at the RNA primer.
The RNA primer is removed and replaced with DNA by polymerase I,
and the gap is sealed with DNA ligase.
Single-stranded DNA-binding (SSB) proteins (>200) stabilize the
single-stranded template DNA during the process.
14. DNA Replication
Replication is continuous on the leading strand and semi
discontinuous on the lagging strand.
Unwinding of single DNA replication fork proceeds in one direction.
The two DNA strands are of opposite polarity, and DNA polymerases
only synthesize DNA 5’ to 3’.
Solution: DNA is made in opposite directions on each template.
Leading strand synthesized 5’ to 3’ in the direction of the
replication fork movement. It continuous requires a single RNA
primer.
Lagging strand synthesized 5’ to 3’ in the opposite direction.
Semi-discontinuous ,it requires many RNA primers , DNA is
synthesized in short fragments.
16. Biological roles
• Pharmaceutical Importance Of Nucleic Acid
Used in cancer, cardiovascular and autoimmune diseases.
The pharmaceutical perspectives of Nucleic acid based therapy
presents a comprehensive account of gene therapy.
Internationally acclaimed scientists discuss the potential use of
lipid, peptides and polymers for the vivo delivery of nucleic
acids.
Control gene regulation, transcription, translation and
replication.
17. Functions Of Nucleic Acids
• Function of DNA (deoxyribonucleic acid)
Permanent storage place for genetic information.
Controls the synthesis of RNA(ribonucleic acid)
The sequence of nitrogenous bases in DNA determines the protein
development in new cells.
The function of the double helix formation of DNA is to ensure that
no disorders occur.
This is because the second identical strand of DNA that runs anti-
parallel to the first is a back up in case of lost or destroyed genetic
information.
Examples: Down’s syndrome or sickle cell Anemia.
18. Functions Of Nucleic Acids
• Functions of RNA(ribonucleic acid):
Synthesized by DNA for the transportation of genetic
information to the protein building apparatus in the cell.
Synthesis of new proteins using the genetic information it has
transported.
mRNA(messenger ribonucleic acid) is used to transfer genetic
information through plasma membranes
RNA also directs the nucleic acid (specially DNA) carry out a vital
role in the human body.
In particular, nucleic acids play an essential role in:
A. Mitosis, Meiosis
B. Providing energy/cellular respiration.
19. Gene Therapy
It is a technique for the correction of a genetic deficiency in a cell by
the addition of new DNA to the cell. This definition has been
expanded to include treatments of acquired diseases by the addition
of new DNA.
There are four approaches:
A normal gene inserted to compensate for a nonfunctional gene.
An abnormal gene traded for a normal gene
An abnormal gene repaired through selective reverse mutation
Change the regulation of gene pairs
20. Gene Therapy Strategies
o Gene Augmentation Therapy (GAT)
o Gene inhibition therapy.
o Gene replacement therapy
o Gene Correction (Chimeraplasty)
o Targeted killing of specific cells
o Prodrug therapy
22. Types of Gene Therapy
• 2 Types of Gene Therapy
Somatic gene therapy involves introducing a “good “ gene into
targeted cells with the end results of treating the patient-not the
future children
Germline gene therapy involves modifying the genes in egg or
sperm cells, which will then pass any genetic changes to future
generations as well
24. Application of gene therapy
Cancers
Inherited disorders
Infectious diseases (viral or bacterial)
Immune system disorders
Vaccination
Diabetes AIDS Cancer Parkinson’s
Disease
25. Cancer Approaches
Delivery of genes encoding toxic molecules to cancer cells to kill
them.
Delivery of genes encoding chemokines to cancer cells to activate the
immune response to recognize and kill them.
Antibody therapies: DNA vaccines with genes that encode antibodies
to cancer specific proteins in tumor cells.
Insertion of normal tumor suppressor genes into cells.
Antisense therapy: DNA that blocks synthesis of proteins encoded by
deleterious genes.
26. Problems with gene therapy
Short Lived.
Hard to rapidly integrate therapeutic DNA into genome .
Would have to have multiple rounds of therapy.
Immune Response.
new things introduced leads to immune response.
increased response when a repeat offender enters.
Viral Vectors.
patient could have toxic, immune, inflammatory response.
also may cause disease once inside.
Multi gene Disorders.
Heart disease, high blood pressure, Alzheimer’s, arthritis and
diabetes are hard to treat because you need to introduce
more than one gene.
27. Requirment for Gene therapy
Understanding of the disease process.
Structure/function of gene to be introduced.
Efficient delivery of gene.
Control of gene expression.
Prevention/control of immune responses.
Animal model and assessment of function.
Clinical trial.
28. Trojan Horse
New technique & first published on 14 Jan,2016.
Origin :
Scientists from “Ohio State University” developed .
Drug-delivery technique called “DNA origami”.
Artificially created DNA binds together to form a tiny capsule.
Previously used for delivery throughout the body,
So 1st time using to attack drug-resistant cancer cells.
29. Basic Concept
“Daunorubicin” (a chemotherapeutic drug) -
Added inside of DNA capsule.
15 nm wide and100 nm long.
About 50,000 times smaller than a five pence piece.
Tucks into the cancer cell's DNA & prevents it from replicating.
Capsule structure given -
To add lots of accessible DNA base-pairs to tuck into.
When broken, the drug molecules are freed to flood the cell.
30. Trojan Horse
The origami structures, both empty (left) and loaded with a chemotherapy drug (right).
31. Experiment & how it works
• Treating “Acute myeloid leukemia (AML)” cells within mice.
with the chemotherapy drug “Daunorubicin”.
• Some cells were entirely resistant to this type of treatment.
• When molecules of this drug enter an AML cell,
They quickly respond.
Pump it back out through small openings of cell walls.
• To overcome this issue,
Conjure up a way without the cell noticing.
DNA will be the best fit.
32. Experiment & how it works
• Created strong, stable, rod-shaped capsules .
Infiltrate the AML cells,
Retrieved from their surroundings as nutrients.
• When a capsule is sufficiently deep inside the cell,
It begins to break down,
Anti-cancer drugs are released.
AML cell can’t react in time to pump the drug back out & died.
• The drug destroyed the cancer cells in under 15 hours.
33. Experiment & how it works
Experiment Result :
Successful trials in mice
Hoping to test their idea in humans.
If it works in humans, there should be no
limit to the type of cancer cell it can be
effective against.
34. Conclusion
When an error occurs in any of the steps involved in
expressing the genetic information contained in DNA a
genetic disease may occur. Understanding how nucleic
acids store and deliver genetic information within the cells
is necessary to understand diseases and to plan
strategies for disease treatment. Many genetic diseases
cannot be cured at the moment, but recognizing the
importance of nucleic acids in these diseases may be the
key that eventually unlocks a cure.