Transgenesis

In the early 1980s, the use of transgenic animals started to soar and was expected to fill the gap between gene discovery and function. Today, animal models are based on classical transgenic animals that exhibit a genetic modification present in all tissues derived from the modified embryos.

There are two classical methods to produce transgenic animals:

• One transgenesis method consists in gene targeting through embryonic stem cells (ES cells) which are genetically transformed. These modified ES cells are microinjected into the cavity of an egg (e.g. a blastocyst composed of an aggregate of cells after 3.5 days of gestation) that is placed in the uterus of female mice. The cells divide and spread to all tissues of the embryos.
• The second method consists in introducing a purified engineered DNA into the pronuclei of fertilized mouse eggs. Injected embryos are surgically implanted into a pseudopregnant foster female uterus and transgenic newborn mice are screened for the presence of the trransgene.

Recently, a lentiviral transgenesis approach has been developped as an alternative to direct microinjection of DNA into pronuclei. In this case, lentiviral vector is injected into the perivitelline space of fertilized mouse oocytes. Vectalys has focused on this approach using highly purified vector batches which greatly increases embryo survival and allows a very high proportion of transgenic founders (>95%) as well as a very efficient transgene transmission to the progeny (>85%).

Although the technological challenges were impressive at that time, now new tools give rise to a new animal concept approach. Vectalys starts a new research program to develop lentiviral vectors transgenesis based methods by generating genetically modified adult animal in targeted tissues only and not in the whole organism. The goal is to generate more reliable models to the real human situation.

Lentiviral vector mediated transgenesis is simple, cheap, and highly efficient. Furthermore, it can take full advantage of the great diversity of lentiviral vectors developed for other applications, and thus allows for ubiquitous or tissue-specific transduction (specific promoter for endothelial cells, neural cells, hepatic cells...), constitutive or externally controllable transgene expression, as well as RNAi-mediated gene knockdown.

Vectalys provides new tools for gene discovery and validation into animals. Vectalys has developed specific serum free purified vectors batches (D) for in vivo injection showing several advantages:

• The Vectalys high vector quality and concentration allow a quicker process to obtain transgenic animal
• The Vectalys patented lentiviral vectors do not affect the viability and the proliferation of your target cells (oocytes).
• Vectalys lentiviral vectors ensure that the integration events occur in every cells – 100% transduction efficiency can be achieved.

At Vectalys, we provide full teams of experts in animal engineering to support you and to fit the best your projects. We will help you to design the best experimental protocol for your gene delivery project.