GENE THERAPY

Experimental technique uses gene to treat or prevent disease

Differ from drug based traditional approach it treats the symptoms but not the underlying genetic
problems
Two types
Germ line therapy
Somatic cell gene therapy
ELIGIBILITY CRITERIA
Could the condition be corrected by adding one or a few functional genes?
Do you know which genes are involved?
Do you understand the biology of the disorder?
Can you deliver the gene to cells of affected tissue?
APPROACHES
Replacing a mutated gene with healthy gene
Inactivating or knocking out a mutated gene
Introducing new gene to fight against disease
PROPERTIES OF THE VECTOR
TARGET the right cells
INTEGRATE the gene in the cells
ACTIVATE the gene
AVOID harmful side effects
VECTORS
VIRAL
Retroviral
Adenovirus
Adenovirus associated virus
Herpes simplex virus
Vaccinia
Baculovirus
Murine leukaemia virus
NON VIRAL
Using liposomes
Injecting plasmid DNA
Anti sense technology
1. Retrovirus
Carry their genetic material in the form of RNA
Ex. HIV AIDS
Target only dividing cells
Maximum length of RNA can be inserted 8 kb
Activation
1. Infect cells RNA into nucleus RNA to DNA by reverse transcriptase
Integration
1. DNA from RNA integrate the human genome in random location duplicates
along with human DNA during cell division
Side effects
1. Random integration disrupts another gene affect the cell division regulation
tumor growth
2. Immune response can prevented by engineering the surface protein
2. Adenovirus
Responsible for common cold
Carries ds-DNA
Targets both dividing and non dividing cells
Maximum length of DNA can be inserted 7.5kb
Infects cell DNA in to nucleus gene activation
No integration into human genome discarded in 1 or 2 week
Immune response is the side effect
3. Adeno associated virus
Dont cause any diseases in human
Carries ss-DNA
Targets dividing and non dividing cells
Need assistance HELPER virus to replicate themselves inside cells
Maximum length of DNA can be inserted 5kb
DNA integrates into human genome 95% in a specific region on chromosome 19
So less chance of disrupting other genes

4. Herpes simplex virus
Targets and infects cells of nervous system
20kb maximum
Dont integrate with human genome
But stay inside cell for longer time
Wont disrupt other genes
Immune response is the SE
NON VIRAL
Plasmid + lipid cover liposome
Virus +liposome virosomes
Can carry large genes
Dont trigger immune response
But less effective than viral vectors
EX VIVO VS
In vivo gene vector injected to patient
Ex vivo gene cells removed from human after activation put back cells in to patient
Ex vivo alternative to bone marrow transplant no need of matching patients own bone marrow
correcting gene re-infuse

ADVANTAGES
Very effective when delivered to tissue correctly.
Can avoid drug side effects.
It fixes the problem at its source.
Gene therapy can eliminate and prevent hereditary diseases.
CHALLENGES
Gene delivery and activation
Wrong target adverse outcome germ line instead of somatic transfer to next generation
Long lasting activation needed
Large number of genes needed in some disorders correct target
Immune response
Unwelcome immune response serious illness and death
Jesse Gelsinger had liver disorder gene therapy trial 1999 died of acute inflammatory
response adenovirus vector
So Ex vivo started
Disrupting important genes in target cells
Gene stiches in inappropriate location ????
Between 1999 and 2006 gene therapy for SCID restore the function of gamma c gene in
cells of immune system
5 children developed leukemia in later life new gene stitched to regulatory gene un
controlled cell division
Commercial availability
Genetic disorders rare
Cant produce in large scale
If do it for single person very costlier than bulk production
1990
September 14 - first approved gene therapy
Prof. William French Anderson National institute of health
4 year old girl Ashanti DeSilva ADA-SCID
2003
University of California liposome coated gene therapy for Parkinsons disease
2006
March - Gene therapy X linked chronic granulomatous disease
August NIH Maryland Metastatic melanoma
November university of Pennsylvania immune therapy with lentiviral vector against HIV
envelope
2007
May 1 moorfields eye hospital and university college London announced first gene
therapy trial for inherited retinal disease Lebers congenital amaurosis
2010
September France successfully treated a beta-thalassemia major case
2011
August university of Pennsylvania pilot study CLL 26/59 complete remission
2012
European medicine agency recommended approval for Alipogene tiparvovec (Glybera)
compensates for lipoprotein lipase deficiency
2013
March Memorial Sloan Kettering cancer center New York - 3/5 ALL patients had been in
remission for 5 month to 2 years after treatment
2014
University of Pennsylvania Choroideremia REP1 gene AAV vector

IGMSY
Every third women is undernourished
Every second women is anaemic
Economic and social distress - Undernourished mother LBW baby
Work till delivery and immediately after delivery poor care on child and poor health to mother
To cover this economic issue compensate wage Ministry of women and child development
introduced Indira Gandhi Matritva Sahyog Yojana (IGMSY) conditional maternity benefit scheme.
OBJECTIVE
To improve health and nutrition of pregnant and lactating women and their young infants by:
1. Promoting appropriate practices, care and service utilization during pregnancy, safe delivery and
lactation
2. Encourage exclusive breast feeding and IYCF
3. Contribute better environment by incentives
BENEFICIARIES
1. Pregnant and lactating women 19 and above
2. first 2 live births
3. All government employees and their wives excluded
4. Age and number of births reported by beneficiary false evidence prosecution
5. Pregnant and lactating AWW and AWH avail the benefits
DISTRICTS UNDER THE SCHEME
1. 52 selected districts through AWCs
2. Districts selected based on six indicators:
1. Female literacy (%)
2. Registration of mother in first trimester (%)
3. At least 3 antenatal visit (%)
4. Institutional births (%)
5. Children (12-23 months) fully immunized (%)
6. Children breast fed with in one hour (%)
Districts divided into good, medium and poor performance based on scores from those indicators.Out of
52 districts 11 from good, 11 from poor and 26 from medium performance and 4 are UTs.100 percent
centrally sponsored
REGISTRATION
Eligible woman has to register herself at the AWC for IGMSY
Every registered mother receive MCP card from AWW or ANM
PAYMENT AND CONDITIONALITY
Payment of Rs.4000 in three installments
JSY benefits during delivery also avail
Cover 40 days wage loss at Rs.100 per day basis
Provide nutritional assistance and rest from work
Rs.1500 at the end of 2
nd
trimester
Under fulfilment of 5 conditions:
Registration of pregnancy within 4 months
At least one antenatal check ups
Received IFA tablets
At least one TT vaccination
Received at least one counseling session at AWC/VHND/Home visit

SECOND
Rs.1500 at the end of 3 months after delivery
Fulfilling 6 conditions
1. Child birth registration
2. Received polio and BCG
3. Polio and DPT -1
4. Polio and DPT-2
5. Child weighed at least two times after birth
6. After delivery mother has attended atleast 2 IYCF counseling sessions.
THIRD
Rs. 1000 infant completes 6 months of age
On fulfilment of 5 conditions:
1. Exclusive breast fed for 6 months
2. Complementary foods on completion of six months
3. Child received Polio and DPT-3
4. Weighed at least two times between 3 months and 6 months
5. Mother attended at least 2 IYCF counseling between 3 and 6 months of lactation.
SPECIAL SITUATIONS
Fulfils first installment condition miscarriage give first installment
If still birth provide 2
nd
installment to attend counseling session
Infant died with in 3 months give 2
nd
installment other than infanticide
First twins only once
Second twin - no problem for second time benefit
Receive benefit from only registered AWCs, even if they delivered some where
VERIFICATION OF CONDITIONALITY
AWW
MCP card
IGMSY register
Growth monitoring register of ICDS
Exclusive breast feeding and initiation of complementary foods are to be self certified
ICDS supervisor:
During field monitoring visits IGMSY/MCP cards
Verify Monthly Progress Report (MPR)
INCENTIVES TO AWW AND AWH
AWW Rs. 200 per beneficiary bank
AWH Rs. 100 per beneficiary bank
All cash disbursement bank/post office no cash or cheque
FLEXI FUNDS
Flexi-fund accounting for 2.5% of total annual expenditure under this scheme available for each
SG/UT for innovative activities
Providing additional incentives state specific issues/problems:
Marriage after 21 years
First child birth after 22 years
Spacing 2-3 years
Child in green zone WHO growth chart
Both children girls
Women with disability
CAPACITY BUILDING AND IEC ACTIVITIES
3 percent of annual expenditure
All staffs sensitized to IGMSY workshops
Training regular job training IGMSY and refresher training
Training of PRI
IEC- pamphlets
Advertisements
INTER DEPARTMENTAL CONVERGENCE
Health department
PRI
Information/public relations department
State and district post office/banks
State training institutes/medical colleges
MONITORING AND SUPERVISION
Along with ICDS
Field visits by state officials/DPO/CDPO/supervisors as per schedule under ICDS
EVALUATION
Baseline and end line surveys- effect of programme
Concurrent evaluation as per GOI maintain uniformity
Social audits and addressing the grievances

KFD