Download Gene therapy and viral vectors - Lectures For UG-5

Gene therapy and viral vectors
Herpes Simplex Virus
Herpes Simplex Virus Type (HSV) is
a double stranded DNA virus that
belongs to Herpesviridae family.
 It contains three main structural
components.
 A central core holds the viral DNA,
an inner core is surrounded by an
envelope that is made of viral
glycoproteins and a capsid.
 The tegument is located between
the capsid and the envelope and
various proteins that are delivered
into the infected cell upon cell
fusion.

The herpes family of viruses consists of three
families
of
viruses;
Alphaherpesviridae,
Betaherpesviridae, and Gammaherpesviridae.
 Among these families are many commonly known
viruses that are causative agents of many diseases,
such as HSV-1 and HSV-2 for cold sores and
genital warts, varicella zoster for chickenpox.
 Herpes virsues also tend to have latent, recurring
infections in the infected organisms, where the
virus remains in some part of the infected
organism.
 Herpes family viruses are incredibly common,
with at least 90% of people within the United
States having been infected with at least one form
of Herpesviridae.

Life Cycle of Herpes Virus

http://www.sumanasinc.com/webcontent/
animations/content/herpessimplex.html
Herpes Simplex Viral Vector
Some of the more important drawbacks
 Immunogenecity of the particle
 Packaging constraints
 Long term maintenance of the genetic
material
 Random integration

Cancer cell therapy with HSV







HSV has many traits that make it desirable as a treatment vector;
HSV can infect a wide variety of cell types,
the normal replication cycle of HSV causes cells to lyse (killing cancerous
cells),
The HSV genome has many genes that are non-essential to replication that
can be replaced with therapeutic genes, there are already many
pharmaceutical options that can be used to control against unwanted
replication of the virus, and the viral genome remains as an intact plasmid
within the cell nucleus which protects against unwanted insertion of viral
DNA into the host genome.
HSV viruses were re-engineered to express cytotoxic genes or genes to
stimulate immune response.
The effectiveness of HSV as a treatment vector increased when used in
conjunction with other cancer therapies such as radiation treatment and
chemotherapy.
Three strains of re-engineered HSV, designated G207, 1716, and NV1020,
were put through Phase I clinical trials in 2002. There were no negative
effects attributed to the virus. These strains were effective in the treatment
of a variety of tumors in mice, including breast, prostate, colon, and
pancreatic cancer, as well as rarer cancers. (Varghese, 2002).
Phases of clinical trial
Population size in clinical trials
Assignment
Group 1: AIDS/HIV
 Group2: Arthritis
 Group 3: Hemophilia
 Group 4: Hypertension
 Group 5: Diabetes
 Group 6: Hepatitis
 Group 7: Cancer (Any type)
 Group 8: Cancer (Any type)

Topics to be covered in the
assignment
Introduction of the disease or disorder
Type(s) of mutations involved
Conventional treatment
Type of vector
The procedure of gene therapy
History of clinical trials
At which phase of clinical trial the treatment
is undergoing?
 Is it commercially available?
 Deadline : 30 Oct






