February 21, 2014: Human Germline Engineering
• Genetically modified humans?
• Gene therapy
o This is the process of using DNAas a therapeutic (in contrast to drug therapy)
o In general, a mutated gene must be fixed by either
Adding the normal gene
Replacing the mutated gene with a normal gene
o Kill cancer cells using genes
o DNAvaccines – genes to combat infectious diseases
o Somatic cell gene therapy [type 1] vs. reproductive (aka germline) gene therapy
Somatic cells: cells derived from the basic germ layers of the body
(endoderm, mesoderm, ectoderm) that DO NOT pass their genetic
information to the next generation
Germ cells: cells that give rise to the gametes and DO pass their genetic
information to the next generation
• Gastrulation forms the basic germ layers of the body and creates
the germ cells for the next generation.
• Two types of delivery for somatic cell gene therapy
o Direct delivery
o Cell-based delivery
Genetically identical iPSCs are generated from the
Adult stem cells are isolated and propagated in the
laboratory. This only works for adult stem cells that
can be isolated, however.
Gene therapy often exploits viruses to deliver genes to cell nuclei.
• Insert a new gene into bits of the virus’DNAand then let the virus
perform its normal actions. • Because the vehicles used are viruses, though, there is some risk,
because the body might recognize them as invaders and destroy
them or develop a strong immune reaction.
Challenges of somatic gene therapy
• Must get therapeutic gene into relevant cells’nucleus
o Direct vs. cell-based delivery
• Genes must be expressed long-term
o Foreign genes tend to be “silenced”
o Gene repair is not perceived as “foreign” but is much more
• Safety concerns unique to somatic gene therapy
o Removal of the engineered cells could prove difficult
o 1999 death due to a massive adverse immune response to
virus put a huge damper on gene therapy in general
o Side effects from integration of foreign DNA
o So far, there has been limited success for somatic cell gene therapy
o Research in somatic cell gene therapy
Development of gene delivery vehicles that do not rely on viruses
New ways to destroy, introduce, or repair genes
• Slide with picture of scissors
Demonstrating treatments in animal models
Using patient-specific iPSCs to correct genetic defects and then creating
the appropriate tissue.
• Remember – iPSCs can be derived from any adult tissue. They are
tricked into thinking they are embryonic and then can be injected
into any offending areas.
Reproductive (germline) gene therapy
• Gene therapy to alter the genetic constitution of germ cells
• Affects all the cells of the body – not targeted to a specific tissue
• Manipulates the genome of a person before he/she is born • Imposes a permanent change that is passed on to subsequent
• Modified version – making “transgenic animals” – animals with an
added gene, not a modification to their existing genes
o Deliver the gene into the nucleus of a fertilized one cell
o Develop to a blastocyte and implant it into a uterus
o Test to verify that the gene is present in the offspring
o To see that it works, florescent proteins are often used –
easy to identify. Then, these animals will be florescent if
the gene is successfully transferred.
o Transgenics work well for “adding” a gene, but to repair or
replace a gene currently requires cells that can be cultured
in a dish.
To do this, you have to catch the person at the one-
cell stage – before he/she really exists.