RNA-based therapies such as mRNA vaccines and ribonucleases are emerging as promising immunotherapies for cancer and infectious diseases. mRNA can be engineered to transiently express proteins and has entered clinical trials for cancer immunotherapies and infectious disease vaccines. Ribonucleases are enzymes that degrade RNA and have cytotoxic effects, making them a potential therapeutic for cancer by selectively targeting and destroying tumor cells. Several RNA-based therapeutics are currently in clinical testing for a range of diseases. mRNA in particular has potential for cost-effective scalable production and for inducing protective immune responses with small doses.
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RNA-Based Cancer and Viral Therapies
1. "Mechanisms of RNAmediated
anticancer and antiviral therapies"
Huda Abbasi (PhD scholar)
Saleha Resham (PhD scholar)
Asim Abbas (MS scholar)
RNA vaccines are finally emerging as immunotherapies to combat pandemics
and cancer
2. • Part of the problem is that RNA has been widely
perceived in the research community as too fragile
and difficult to work with. “RNA is not a stable
molecule, it’s been designed to be unstable,
hydrolyzed, and there are RNAses everywhere.
• All of that is true, but it’s controllable, and it’s not
going to be an issue pharmaceutically,”
3. THERAPEUTIC
VERSATALITYOF
RNA
mRNA
In vitro transcribed m-RNA(IVT) has recently come
into focus as potential new drug class to deliver
genetic information. Such synthetic m-RNA can be
engineered to transiently express proteins by
structurally resembling m RNA.
IVT m RNA, based cancer immunotherapies and
infectious disease vaccines have entered clinical
development
Ribonuclease
Ribonucleases (RNAses) are small molecules which are
highly cytotoxic in nature.
They catalyze the degradation of RNA into smaller
molecules rapidly in an unprotected environment.
4. Promise holding
for both,
therapeutics,
infectious disease
and cancer
RNA vaccines rely on a different way to mimic
infection. Compared to previous vaccines, this
method is more robust, more versatile, and yet,
equally efficient. Therefore, the RNA vaccine
technology holds great promise to prevent and
treat a wide range of diseases, such as influenza or
cancer.
The Bill & Melinda Gates Foundation and
CureVac today announced that the foundation
has made a commitment to invest $52 million
(€46 million) in CureVac, a leading clinical-stage
biopharmaceutical company specializing in
mRNA-based vaccine technologies.
The Bill & Melinda Gates
Foundation
8. Biological
activities
• Ability to catalyze cleavages of phosphodiester bonds
in cellular RNA
• Maturation of mRNA and non-coding RNA
• Apoptosis induction
• Protection against viral infections
A super family of enzymes
which catalyze the
degradation of RNA by
operating at the level of
transcription & translation
RNAses
9. RNASESASAN
ALTERNATIVE
TO
CHEMOTHERA
PY
The RNAses as antitumor drugs or therapeutic agents
have the ability to eliminate the tumor cells.
RNAse cytotoxic effects are based on selective
hydrolysis of RNA, selective intracellular routing and
membrane-specific recognition processes.
The cytotoxic pathways of RNAses can be used as
working platform for the creation of new anticancer
drugs.
11. kill with kindness
Kanwar, S. S., & Kumar, R. (2017). Ribonuclease as Anticancer Therapeutics. Enz Eng, 6(162), 2.
Bovine seminal
ribonuclease
(BR- RNAse)
Onconase
RNAse T1
α-Sarcin RNAse T2 RNAse P
RNAse Sa
bind to cell
membrane and
enter cytosol to
degrade the
natural cytoplasmic
RNA
Degrades tRNA
and inhibits protein
synthesis
Activates caspases
induces apoptosis
12. A scheme of potential interactions of cytotoxic RNAse with host
• RNAse binds on to the cell
membrane by lipid rafts or receptor.
• Internalizes into the cytosol by
endocytosis and targets to the motif
in RNA or Ras-protein causing
degradation of RNA into
nucleotides.
• This leads to alteration of gene
expression (blocks the protein
synthesis).
• Alteration of gene expression helps
to activate the Caspasesdriven cellKanwar, S. S., & Kumar, R. (2017). Ribonuclease as Anticancer Therapeutics. Enz Eng, 6(162), 2.
13. How Cancerous cell is differentiated from normal cell?
ER
Golgi App
TACA
The cancer cell
surface is more
anionic than
normal cell due
to these
larger
exposures of
membrane
bounded
glycosaminogly
can profile,
phospholipid,
and
glycosphingolip
id
In normal cells,
proteins are
glycosylated for
normal function
In Cancerous cells,
hyperglycosylated
proteins are not
further processed
and, are displayed
on cell surface
TACA = Tumor associated carbohydrate antigens
14. Action of RNAse on Cancerous cell
RNA
Cell Death
The RNAse molecule
binds to the cancerous
cell components
(Glycans or heparin-
sulphate proteoglycan,
lipid raft etc. which
act
as receptors) due to
Columbic interactions
TACA
- - - -
RNAse is endocytosed into
Cancerous cell
16. CONCLUSION
RNA is an emerging therapeutic tool in medicine.
While different types of RNA and RNA-associated
molecules can be used, mRNA and ribonuclease based
therapeutics have been widely studied for both cancer
and infectious diseases.
Several RNA-based therapeutics are currently under
clinical investigation for diseases ranging from genetic
disorders to HIV infection to various cancers.
17. (i)
It is a non-integrating non-
infectious gene vector that
can be readily designed to
express any protein with high
efficiency
(ii)
It has the potential for cost-
effective highly scalable
manufacturing
(iii)
Small doses are sufficient to
induce protective immune
responses.
mRNA has emerged as a promising vaccine modality that can elicit
potent immune response , while
avoiding the safety risks
anti-vector immunity associated with some live virus vaccines.
Vaccination with mRNA offers several advantages over other vaccine
platforms:
Vaccination with mRNA offers several advantages over
other vaccine platforms:
RNA vaccines represent a promising alternative to conventional vaccine approaches because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration .
their application has until recently been restricted by the instability and inefficient in vivo delivery of mRNA.
Recent technological advances have now largely overcome these issues, and multiple mRNA vaccine platforms against infectious diseases and several types of cancer have demonstrated encouraging results in both animal models and humans
There’s a preconception that RNA is not a stable molecule, it’s been designed to be unstable, hydrolyzed, and there are RNAses everywhere.
All of that is true, but it’s controllable, and it’s not going to be an issue pharmaceutically,”
therapeutic ribozymes, aptamers, and small interfering RNAs (siRNAs),
Sahin, U., Kariko, K. & Tureci, O. mRNA-based therapeutics — developing a new class of drugs. Nat. Rev. Drug Discov. 13, 759–780 (2014).
RNAses are a super family of enzymes which catalyze the degradation
of RNA by operating at the level of transcription, protein synthesis and
thus play key roles in the regulation of vital processes in any organism
ranging from virus to human [1]. It is a type of nuclease which has the
ability to catalyze cleavages of phosphodiester bonds in cellular RNA
and also possess the biological activities like the maturation of mRNA
and non-coding RNA, RNA interference, apoptosis induction and
protection against viral infections these all process were not possible
without RNA degradation
RNAses are a super family of enzymes which catalyze the degradation
of RNA by operating at the level of transcription, protein synthesis and
thus play key roles in the regulation of vital processes in any organism
ranging from virus to human [1]. It is a type of nuclease which has the
ability to catalyze cleavages of phosphodiester bonds in cellular RNA
and also possess the biological activities like the maturation of mRNA
and non-coding RNA, RNA interference, apoptosis induction and
protection against viral infections these all process were not possible
without RNA degradation