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Surface-mediated targeting of lentiviral vectors

Published on August 5, 2014   29 min

A selection of talks on Infectious Diseases

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0:00
This is Christian Buchholz at the Molecular Biotechnology and Gene Therapy section at the Paul-Ehrlich Institute in Langen, Germany. I'm very pleased to present the lecture on surface-mediated targeting of lentiviral vectors.
0:15
I have divided the lecture into the topics listed here. We'll start with an introduction into surface targeting of immuno viruses. I will then show you a series of examples covering a broad variety of target subtypes, including lymphocytes, hematopoietic stem cells, neurons, and endothelial cells. We will first focus on ex vivo applications and then go through some examples of in vivo administrations of the targeted vectors.
0:42
In gene therapy, we do basically distinguish between in vivo and ex vivo modification of target cells. By in vivo, we mean that vectors are directly injected into the patient, which can be locally, such as intracerebrally, or systemically. Ex vivo means that target cells are removed from the patient then transduced ex vivo in culture vessels before they will be re-implanted into the patient. It is obvious that upon in vivo applications, vectors will encounter a large variety of cell types besides the actual target cells relevant for therapy. However, also ex vivo, primary cells are not homogeneous and may well differ, for example, in the differentiation state. Targeting vector particles to the relevant cell type without losing particles to non-relevant cells is therefore an important goal in vector engineering. Only surface targeting of vector particles may make this possible.
1:38
To understand the strategies to achieve surface targeting, we first have to look at the entry routes of retroviral vectors. Retroviral vectors are envelope particles that bind with their surface receptor for cell entry. Both entry modes, pH-independent on the left, and pH-dependent on the right, the barrier of particle actin has to be passed. We will actually come back to this later in this lecture. Moreover, in each entry mode, fusion of the viral and the cellular membranes, which is the plasma membrane in A and the endosomal membrane in B, is required to release the genetic information into the cell. This is a tightly regulated process which can be induced by low pH or, as in the case of anti-viruses and also measles virus, by receptor contact. The molecular basis behind this is illustrated on the next slide.

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Surface-mediated targeting of lentiviral vectors

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