oligonucleotides,DNA,RNA,NUCLEOTIDES,ANTISENCE OLIGONUCLEOTIDES,APTAMERS

1. (OLIGONUCLEOTIDES)
GAURAV BHARDWAJ
1901990566004
M.PHARM 2ND SEM.
Under The Guidence Of
Dr.Ashu Mittal Sir

2. CONTENTS
Oligonucleotides:
Introduction
DNA & RNA
Nucleotides
Oligonucleotide Drug Delivery
Drug Delivery strategies
Modes of Action
Advantages and limitations
Applications
References

3. INTRODUCTION-
Oligonucleotides are short DNA or RNA molecules.
 Greek “oligo” – Few or small
 OR oligonucleotides are short sequences of nucleotides
(DNA/RNA).
Nucleotides are the building blocks of nucleic acid.
Nucleotide having 3- sub units.
Nitrogen base
ribose(5-c sugar)
one phosphate group
Polynucleotides is a bipolymer,composed of 13 or more
nucleotides monomer (bonded with covelent bond).
Eg.DNA,RNA

4. The length of the oligonucleotide is usually denoted by
"mer" (from Greek meros, "part").
For example- an oligonucleotide of six nucleotides (nt) is a
hexamer, while one of 25 nt would usually be called a "25-
mer".

5. DIFFERENCES IN DNA AND RNA STRUCTURE

6. NUCLEOSIDES AND NUCLEOTIDES
Nucleotides are phosphorylated
derivatives of nucleosides.
A nucleotide is formed when a
phosphate group is attached
either 3’C or 5’C of pentose
residue of nucleoside.

7. OLIGONUCLEOTIDE DRUG DELIVERY
 Strategy of therapeutic oligonucleotides is divided into
four categories, as follows:
A) Single piece of oligonucleotide
B) Oligonucleotide-ligand conjugate
C) Oligonucleotide-polymer conjugate
D) Nanoparticle

9. OLIGONUCLEOTIDE DRUG DELIVERY CATEGORY-
Therapeutic oligonucleotides, on the basic of mechanism of
action is divided into 2 categories, as follows:
A) Antisense Oligonucleotides
B) Modulator of protein activity (Aptamers)
A) ANTISENSE OLIGONUCLEOTIDES
 Many pharmacological approach involve creating
compounds that binds and disable protein.
Eg. Proponolol, Cimitidine
A new way to block protein function is to prevent translation
of mRNA into protein.
An Antisense oligonucleotide therapy is one such approach
which blocks protein formation by inhibiting translation step.

10. Antisense oligonucleotides are the molecules made of
synthetic genetic material, which interacts with the natural
genetic material that codes the information for production of
proteins.
Eg. vitravene (1st antisense
Oligonucleotide drug)
It is targeted to cytomegalovirus.

12. MOA : Antisense technology

13. B) Modulator of protein activity (APTAMERS)
Aptamers (Aptus- to fit, mer- smallest unit of repeating
structures) Based on their 3-dimensional structure, Aptamers
can well fittingly bind to a wide variety of targets from single
molecules to complex target mixtures or whole organisms.
 Single stranded folded oligonucleotides and peptide that
bind to molecular (protein) targets with high affinity and
specificity.
Range in size from 20 to 80 bases (6-26 kDa)

16.  Advantages-
1. Oligonucleotides can be manufactured quickly i.e.
within a week
2. Sensitivity of therapy can be easily measured.
3. Potential of producing longer lasting responses.
4. Potential for enhanced binding affinity to target.

17. Limitations-
 Antisense agents have to be protected against
nucleolytic attack.
The pharmacokinetic characteristics of
oligonucleotide drugs is similar to that of naturally
occurring nucleic acids, makes them poor
therapeutic candidates, as they are immediately
degraded in vivo by nucleases and do not have
adequate pharmacokinetic properties.
 Larger dose are required for therapeutic response.
 The difficulty in directing to a particular cells.
The half-life in plasma is short.

18. APPLICATIONS OF ANTISENS
OLIGONUCLEOTIDE
 The Major areas of these theraputic applications includes:
Antiviral
Antibacterial
CNS theraputics

19. Oligonucleotides also plays important role in-
 DNA sequencing: Determination of nucleotide
sequence in DNA molecule.
 PCR: In-vitro technique of generating large
quantity of specified target DNA.
 Artificial gene synthesis (DNA printing)
 Library construction of DNA
 Molecular Cloning: introducing recombinant DNA
molecule and direct their replication within host
organism.
 Genetic testing, research and forensics.

20. REFERENCES-
 U. Satyanarayana, U. Chakrapani, “Biochemistry” 5th Ed.
(2017), Elsevier.
 P .S. Verma, V .K. Agarwal, “Cell Biology: Cytology
Biomolecules and Molecular Biology” 1st Ed. (2016), S. Chand
and Company Pvt. Ltd.
 Yutaro Asami, Kotaro Yoshioka, Kazutaka Nishina, Tetsuya
Nagata, Takanori.
Yokota* “Drug delivery system of therapeutic
oligonucleotides” Drug Discoveries & Therapeutics. 2016;
10(5):256-262.
Shargel leon,pong-wu susanna,yu b.c.andrew
“pharmacokinetics and biopharmaceutics” ,5th international
edition (2005) pg no.561-562

21. THANKS FOR YOUR
ATTENTION