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Adenovirus Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from t ...
varieties have been explored extensively as a
viral vector A viral vector is a modified virus designed to gene delivery, deliver genetic material into cell (biology), cells. This process can be performed inside an organism or in cell culture. Viral vectors have widespread applications in basic research, ...
for
gene therapy Gene therapy is Health technology, medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells. The first attempt at modifying human DNA ...
and also as an
oncolytic virus An oncolytic virus is a virus that preferentially infects and kills cancer cells. As the infected cancer cells are destroyed by oncolysis, they release new infectious virus particles or virions to help destroy the remaining tumour. Oncolytic vi ...
. Of the many different viruses being explored for oncolytic potential, an adenovirus was the first to be approved by a regulatory agency, the genetically modified H101 strain. It gained regulatory approval in 2005 from China's State Food and Drug Administration (SFDA) for the treatment of head and neck cancer.


Engineering of oncolytic adenovirus

Adenoviruses have so far been through three generations of development. Some of the strategies for modification of adenoviruses are described below.


Attenuation

For adenovirus replication to occur, the host cell must be induced into
S phase S phase (Synthesis phase) is the phase of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. Since accurate duplication of the genome is critical to successful cell division, the processes that occur during S ...
by viral proteins interfering with cell cycle proteins. The adenoviral E1A gene is responsible for inactivation of several proteins, including
retinoblastoma Retinoblastoma (Rb) is a rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissue of the eye. It is the most common primary malignant intraocular cancer in children, and 80% of retinoblastoma cas ...
, allowing entry into S-phase. The adenovirus E1B55kDa gene cooperates with another adenoviral product, E4ORF6, to inactivate
p53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...
, thus preventing
apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
. It was initially proposed that an adenovirus
mutant In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It i ...
lacking the E1B55kDa gene, ''dl1520'' (ONYX-015), could replicate selectively in
p53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...
deficient cells. A conditionally replicative adenovirus (CRAd) with a 24
base pair A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both DNA ...
deletion in the
retinoblastoma Retinoblastoma (Rb) is a rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissue of the eye. It is the most common primary malignant intraocular cancer in children, and 80% of retinoblastoma cas ...
-binding domain of the E1A
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
(''Ad5- Δ24E3''), is unable to silence retinoblastoma, and therefore unable to induce S-phase in host cells. This restricts ''Ad5-Δ24E3'' to replication only in proliferating cells, such as tumour cells.


Targeting

The most commonly used group of adenoviruses is
serotype A serotype or serovar is a distinct variation within a species of bacteria or virus or among immune cells of different individuals. These microorganisms, viruses, or Cell (biology), cells are classified together based on their shared reactivity ...
5 (Ad5), whose binding to
host A host is a person responsible for guests at an event or for providing hospitality during it. Host may also refer to: Places * Host, Pennsylvania, a village in Berks County * Host Island, in the Wilhelm Archipelago, Antarctica People * ...
cells is initiated by interactions between the cellular
coxsackie virus and adenovirus receptor Coxsackievirus and adenovirus receptor (CAR) is a protein that in humans is encoded by the ''CXADR'' gene. The protein encoded by this gene is a type I membrane receptor for group B coxsackie viruses and subgroup C adenoviruses. CAR protein is ...
(CAR), and the knob domain of the adenovirus coat protein trimer. CAR is necessary for adenovirus infection. Although expressed widely in
epithelial cell Epithelium or epithelial tissue is a thin, continuous, protective layer of Cell (biology), cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial (Mesothelium, mesothelial) tissues line ...
s, CAR expression in tumours is extremely variable, leading to resistance to Ad5 infection. Retargeting of Ad5 from CAR, to another receptor that is ubiquitously expressed on cancer cells, may overcome this resistance. * Adapter molecules :Bi-specific adapter molecules can be administered along with the virus to redirect viral coat protein tropism. These molecules are
fusion protein Fusion proteins or chimeric (kī-ˈmir-ik) proteins (literally, made of parts from different sources) are proteins created through the joining of two or more genes that originally coded for separate proteins. Translation of this '' fusion gene'' ...
s that are made up of an
antibody An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...
raised against the knob domain of the adenovirus coat protein, fused to a natural
ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...
for a cell-surface receptor. The use of adapter molecules has been shown to increase viral transduction. However, adapters add complexity to the system, and the effect of adapter molecule binding on the stability of the virus is uncertain. * Coat-protein modification :This method involves genetically modifying the fiber knob domain of the viral coat protein to alter its specificity. Short
peptide Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...
s added to the
C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...
end of the coat protein successfully altered viral tropism. The addition of larger peptides to the C-terminus is not viable because it reduces adenovirus integrity, possibly due to an effect on fiber trimerisation. The fiber protein also contains an HI-loop structure, which can tolerate peptide insertions of up to 100 residues without any negative effects on adenovirus integrity. An RGD motif inserted into the HI loop of the fiber knob protein, shifts specificity toward
integrin Integrins are transmembrane receptors that help cell–cell and cell–extracellular matrix (ECM) adhesion. Upon ligand binding, integrins activate signal transduction pathways that mediate cellular signals such as regulation of the cell cycle, o ...
s, which are frequently over-expressed in
oesophageal adenocarcinoma Esophageal cancer (American English) or oesophageal cancer (British English) is cancer arising from the esophagus—the food pipe that runs between the throat and the stomach. Symptoms often include difficulty in swallowing and weight loss. Ot ...
. When combined with a form of non-transductional targeting, these viruses proved to be effective and selective therapeutic agents for Oesophageal Adenocarcinoma. * Transcriptional targeting :This approach takes advantage of deregulated promoter to drive and control the expression of adenoviral genes. For instance,
Cyclooxygenase-2 Cyclooxygenase-2 (COX-2), also known as prostaglandin-endoperoxide synthase 2 ( HUGO PTGS2), is an enzyme that in humans is encoded by the ''PTGS2'' gene. In humans it is one of three cyclooxygenases. It is involved in the conversion of arachid ...
enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
(Cox-2) expression is elevated in a range of cancers, and has low liver expression, making it a suitable tumour-specific promoter. ''AdCox2Lluc'' is a CRAd targeted against
oesophageal adenocarcinoma Esophageal cancer (American English) or oesophageal cancer (British English) is cancer arising from the esophagus—the food pipe that runs between the throat and the stomach. Symptoms often include difficulty in swallowing and weight loss. Ot ...
by placing the early genes under the control of a Cox-2 promoter (adenoviruses have two early genes, E1A and E1B, that are essential for replication). When combined with transductional targeting, ''AdCox2Lluc'' showed potential for treatment of Oesophageal Adenocarcinoma. Cox-2 is also a possible tumour-specific promoter candidate for other cancer types, including ovarian cancer. :A suitable tumour-specific promoter for
prostate cancer Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...
is prostate-specific
antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
(PSA), whose expression is greatly elevated in prostate cancer. CN706 is a CRAd with a PSA tumour-specific promoter driving expression of the adenoviral E1A gene, required for viral replication. The CN706 titre is significantly greater in PSA-positive cells. * Post-Transcriptional detargeting :Another layer of regulation that has emerged to control adenoviral replication is the use of
microRNA Micro ribonucleic acid (microRNA, miRNA, μRNA) are small, single-stranded, non-coding RNA molecules containing 21–23 nucleotides. Found in plants, animals, and even some viruses, miRNAs are involved in RNA silencing and post-transcr ...
s (miRNA) artificial target sites or miRNA response elements (MREs). Differential expression of miRNAs between healthy tissues and tumors permit to engineer oncolytic viruses in order to have their ability to replicate impaired in those tissues of interest while allowing its replication in the tumor cells. Arming with Transgenes To enhance the efficacy, therapeutic transgenes are integrated into oncolytic adenovirus *stimulation of immune response Immunostimulatory genes Like interferon α (IFNα), tumor necrosis factor alpha (TNFα), and interleukin 12 (IL-12) have been integrated into oncolytic adenovirus to enhance immune response inside the tumor microenvironment. When these molecules selectively expressed in tumor cells, oncolytic adenoviruses promote immune responses against tumor and minimize systemic side effects *Enhancement of Ag presentation Oncolytic adenoviruses have been genetically modified with transgene encoding for granulocyte-macrophage colony-stimulating factor (GM-CSF) to enhance tumor antigens presentation by antigen-presenting cells (APCs). This approach aims to improve recognition of tumor by T-cell and subsequent immune responses, *Targeting costimulatory and Immune Checkpoints on T-cells Oncolytic adenoviruses have been genetically engineered to express checkpoint inhibitors (CTLA-4, anti-PD-L1 antibodies) to release brake of T-cell activity, and to express costimulatory molecules (CD40L, 4-1BBL) to augment T-cell activation and proliferation,


Examples


Oncorine (H101)

H101 and the very similar Onyx-015 have been engineered to remove a viral defense mechanism that interacts with a normal human gene ''
p53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...
'', which is very frequently dysregulated in cancer cells. Despite the promises of early ''in vivo'' lab work, these viruses do not specifically infect cancer cells, but they still kill cancer cells preferentially. While overall survival rates are not known, short-term response rates are approximately doubled for H101 plus chemotherapy when compared to chemotherapy alone. It appears to work best when injected directly into a tumour, and when any resulting fever is not suppressed. Systemic therapy (such as through infusion through an intravenous line) is desirable for treating metastatic disease. It is now marketed under the brand name Oncorine.


dl1520 (Onyx-015)

dl1520 is an experimental oncolytic virus created by genetically engineering a human adenovirus. Onyx Pharmaceuticals used dl1520 under the brand name ONYX-015 in clinical trials as a possible treatment for cancer. This virus, an Ad2/Ad5 recombinant, contains two E1B-55kDa gene mutations allowing the virus to selectively replicate in and lyse p53-deficient cancer cells.


Directed Evolution

Traditional research has focussed on species C Adenovirus serotype 5 (Ad5) for creating
oncolytic An oncolytic virus is a virus that preferentially infects and kills cancer cells. As the infected cancer cells are destroyed by oncolysis, they release new infectious virus particles or virions to help destroy the remaining tumour. Oncolytic vir ...
vaccines for the potential use as cancer treatment. However, recent data suggests that it may not be the best virus serotype for deriving all oncolytic agents for treating human malignancies. For example, oncolytic vaccines based on the Ad5 serotype have relatively poor clinical efficacy as monotherapies. The need for increased potency (infectivity and lytic activity) has led to an expanded search involving a larger number of less well studied adenovirus serotypes.


ColoAd1

One non-species C oncolytic
adenovirus Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from t ...
currently in development is
ColoAd1 Enadenotucirev is an investigational oncolytic virus that is in clinical trials for various cancers. It is an oncolytic A11/Ad3 Chimeric Group B Adenovirus, previously described as ColoAd1. Enadenotucirev has also been modified with additiona ...
. It was created using a process of “directed evolution”. This involves the creation of new viral variants or serotypes specifically directed against tumour cells via rounds of directed selection using large populations of randomly generated recombinant precursor viruses. The increased
biodiversity Biodiversity is the variability of life, life on Earth. It can be measured on various levels. There is for example genetic variability, species diversity, ecosystem diversity and Phylogenetics, phylogenetic diversity. Diversity is not distribut ...
produced by the initial
homologous recombination Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in Cell (biology), cellular organi ...
step provides a large random pool of viral candidates which can then be passed through a series of selection steps designed to lead towards a pre-specified outcome (e.g. higher tumor specific activity) without requiring any previous knowledge of the resultant viral mechanisms that are responsible for that outcome. One particular application of this approach produced ColoAd1, which is a novel Ad11p/Ad3 chimeric Group B oncolytic virus with specificity for human
colon cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel ...
and a broad spectrum of anti-cancer activity in common solid tumours. The therapeutic efficacy of ColoAd1 is currently being evaluated in three ongoing clinical trials (see the EU Clinical Trials Register for further details). ColoAd1 potency can be further enhanced via the use of therapeutic transgenes, which can be introduced into the ColoAd1 genome without compromising the selectivity or activity of the virus. Recent studies with ColoAd1 have shown a unique mechanism of cell death similar to Oncosis with expression of inflammatory cell death markers and cell membrane blistering and have highlighted mechanisms by which ColoAd1 alters host cell metabolism to facilitate replication.


Background

Tumour A neoplasm () is a type of abnormal and excessive growth of tissue (biology), tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tiss ...
s form in
cell Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a de ...
s when
mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...
in
genes In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
involved in
cell cycle The cell cycle, or cell-division cycle, is the sequential series of events that take place in a cell (biology), cell that causes it to divide into two daughter cells. These events include the growth of the cell, duplication of its DNA (DNA re ...
control and
apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
accumulate over time. Most tumours studied, have defects in the
p53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...
tumor suppressor A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell (biology), cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results ...
pathway. p53 is a
transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...
that plays a role in
apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
, cell cycle and
DNA repair DNA repair is a collection of processes by which a cell (biology), cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is cons ...
. It blocks cell progression in response to cellular stress or DNA damage. Many viruses replicate by altering the cell cycle and exploiting the same pathways that are altered in cancer cells. E1B proteins produced by adenoviruses protect the infected cell by binding to and degrading the p53 transcription factors, preventing it from targeting the cell for apoptosis. This allows the virus to replicate, package its genome,
lyse Lyse may refer to: People * Lyse Doucet (born 1939), Canadian journalist, presenter and correspondent for BBC World Service radio and BBC World television * Lyse Richer (born 1958), Canadian administrator and music teacher * Carl L. Lyse (1899– ...
the cell and spread to new cells. This gave rise to the idea that an altered adenovirus could be used to target and eliminate cancer cells.
Onyx-015 Adenovirus varieties have been explored extensively as a viral vector for gene therapy and also as an oncolytic virus. Of the many different viruses being explored for oncolytic potential, an adenovirus was the first to be approved by a regulator ...
is an adenovirus that was developed in 1987 with the function of the E1B gene
knocked out A knockout (abbreviated to KO or K.O.) is a fight-ending, winning criterion in several full-contact combat sports, such as boxing, kickboxing, Muay Thai, mixed martial arts, karate, some forms of taekwondo and other sports involving striking, a ...
, meaning cells infected with Onyx-015 are incapable of blocking p53's function. If Onyx-015 infects a
normal Normal(s) or The Normal(s) may refer to: Film and television * ''Normal'' (2003 film), starring Jessica Lange and Tom Wilkinson * ''Normal'' (2007 film), starring Carrie-Anne Moss, Kevin Zegers, Callum Keith Rennie, and Andrew Airlie * ''Norma ...
cell, with a functioning ''p53'' gene, it will be prevented from multiplying by the action of the p53 transcription factor. However, if Onyx-015 infects a p53 deficient cell it should be able to survive and replicate, resulting in selective destruction of cancer cells.


Clinical trials

There are as of 2023 several ongoing and finished clinical trial testing oncolytic adenoviruses.
ColoAd1 Enadenotucirev is an investigational oncolytic virus that is in clinical trials for various cancers. It is an oncolytic A11/Ad3 Chimeric Group B Adenovirus, previously described as ColoAd1. Enadenotucirev has also been modified with additiona ...
from PsiOxus Therapeutics has entered Phase I/II clinical study with its oncolytic vaccine. Phase I of the trial recruited patients with metastatic solid tumors and showed evidence for virus replication within tumour sites after intravenous delivery. The second phase of the ColoAd1 study will involve the comparison of intra-tumoural versus intravenous injection to examine viral replication, viral spread, tumour necrosis and anti-tumoural immune responses (see the EU Clinical Trials Register for further details).


ONYX-015 (''dl''1520)/H101

Patents for the therapeutic use of
ONYX-015 Adenovirus varieties have been explored extensively as a viral vector for gene therapy and also as an oncolytic virus. Of the many different viruses being explored for oncolytic potential, an adenovirus was the first to be approved by a regulator ...
are held by ONYX Pharmaceuticals and it was used in combination with the standard chemotherapeutic agents
cisplatin Cisplatin is a chemical compound with chemical formula, formula ''cis''-. It is a coordination complex of platinum that is used as a chemotherapy medication used to treat a number of cancers. These include testicular cancer, ovarian cancer, c ...
and
5-fluorouracil Fluorouracil (5-FU, 5-fluorouracil), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stoma ...
to combat head and neck tumours. Onyx-015 has been extensively tested in clinical trials, with the data indicating that it is safe and selective for cancer. However, limited
therapeutic effect Therapeutic effect refers to the response(s) after a treatment of any kind, the results of which are judged to be useful or favorable. This is true whether the result was expected, unexpected, or even an unintended consequence. An adverse effect (i ...
has been demonstrated following injection and systemic spread of the virus was not detected. ''ONYX-015'' when combined with
chemotherapy Chemotherapy (often abbreviated chemo, sometimes CTX and CTx) is the type of cancer treatment that uses one or more anti-cancer drugs (list of chemotherapeutic agents, chemotherapeutic agents or alkylating agents) in a standard chemotherapy re ...
, however, proved reasonably effective in a proportion of cases. During these trials a plethora of reports emerged challenging the underlying p53-selectivity, with some reports showing that in some cancers with a wild-type p53 ONYX-015 actually did better than in their mutant p53 counterparts. These reports slowed the advancement through Phase III trials in the US, however recently China licensed ''ONYX-015'' for therapeutic use as ''H101''. Further development of Onyx-015 was abandoned in the early 2000s, the exclusive rights being licensed to the Chinese company, Shanghai Sunway Biotech. On November 17, 2005, the Chinese
State Food and Drug Administration The National Medical Products Administration (NMPA; ) is a national bureau responsible for drug supervision under the State Council of China and is managed by the State Administration for Market Regulation. History The agency had multiple fo ...
approved H101, an oncolytic adenovirus similar to Onyx-015 (E1B-55K/E3B-deleted), for use in combination with chemotherapy for the treatment of late-stage refractory
nasopharyngeal cancer Nasopharyngeal carcinoma (NPC), or nasopharynx cancer, is the most common cancer originating in the nasopharynx, most commonly in the postero-lateral nasopharynx or pharyngeal recess ( fossa of Rosenmüller), accounting for 50% of cases. NPC occur ...
. Outside of China, the push to the clinic for ''ONYX-015'' has been largely been discontinued for financial reasons and until a ''real'' mechanism can be found.


See also

*
Oncolytic virus An oncolytic virus is a virus that preferentially infects and kills cancer cells. As the infected cancer cells are destroyed by oncolysis, they release new infectious virus particles or virions to help destroy the remaining tumour. Oncolytic vi ...
* Oncolytic AAV *
Oncolytic herpes virus Many variants of herpes simplex virus have been considered for viral therapy of cancer; the early development of these was thoroughly reviewed in the journal ''Cancer Gene Therapy'' in 2002. This page describes (in the order of development) th ...
*
Virotherapy Virotherapy is a treatment using biotechnology to convert viruses into therapeutic agents by reprogramming viruses to treat diseases. There are three main branches of virotherapy: anti-cancer oncolytic viruses, viral vectors for gene therapy and ...


References

{{Reflist, 2


External links


Information about Oncolytic adenovirus
Experimental cancer treatments Adenoviridae Virotherapy Biotechnology