A remote control for gene transfer

Date:
June 17, 2021
Source:
University of Freiburg
Summary:
Researchers develop technology to introduce genes into single
cells in a targeted manner.



FULL STORY ==========================================================================
The ability to insert desirable genes into animal or human cells is
the basis of modern life science research and of widespread biomedical applications. The methods used to date for this purpose are mostly non-specific, making it difficult for scientists to control which cell
will or will not take up a gene.

For this gene transfer, the target genes are often packaged into "viral vectors." These are viruses in which part of the genetic material has
been replaced by the target genes. When researchers add these viral
vectors to cells, the vectors introduce the genes into the cells. This
is the principle behind some of the current SARS-CoV-2 vaccines such as
those from AstraZeneca or Johnson&Johnson. However, it is difficult --
even impossible -- to control into which cells the target genes enter,
since the viral vectors tend to dock non-specifically onto all cells of a certain cell type. A team of researchers from the Cluster of Excellence
CIBSS -- Centre for Integrative Biological Signalling Studies at the
University of Freiburg, led by Dr. Maximilian Ho"rner, Prof. Dr. Wolfgang Schamel and Prof. Dr. Wilfried Weber, has developed a new technology
that enables them to introduce target genes in a controlled manner and
thereby control processes in individual selected cells. The researchers
have published their work in the current issue of Science Advances.


========================================================================== Alteration to a viral vector In their new method, the Freiburg researchers introduce the genetic information with an optical remote control. As
a result, only cells that are illuminated with red light take up the
desired genes. To do this, the scientists modified a type of viral vector
known as an AAV vector, which is already in clinical use.

"We took away the viral vector's ability to dock with cells," Ho"rner
explains, "which is an essential step before the genetic material can
be introduced." To enable this control by light, the researchers have
taken a red light photoreceptor system from the plant Arabidopsis
thaliana (thale cress). This system consists of two proteins, PhyB
and PIF, which bind to each other as soon as PhyB is illuminated with
red light. The Freiburg team placed the protein PIF on the surface of
the viral vector and modified the other protein PhyB so that it could
bind to human cells. Once this modified vector, called OptoAAV, is in
a cell culture along with the cell-binding protein, the protein binds
to all cells. "If a selected cell is now illuminated with red light,
the modified vector can bind to this cell and introduce the target genes
into the illuminated cell," Ho"rner explains.

A key aspect of biological signal research This new approach allows the researchers to introduce target genes into the desired cells within
a tissue culture. The scientists also succeeded in illuminating the
tissue culture successively at different locations, thus enabling the
targeted introduction of different genes into different cells within
a culture. With this technique, it is now possible to control desired
processes in individual cells. This is essential for understanding how
a single cell communicates with cells in its environment, for example,
to control the development or regeneration of an organ. "As these viral
vectors become more widely used in the therapeutic field," Weber says,
"we think this new technology has the potential to make such biomedical applications more precise." Cluster of Excellence CIBSS -- Centre for Integrative Biological Signalling Studies Researchers in the Cluster
of Excellence CIBSS -- Centre for Integrative Biological Signalling
Studies at the University of Freiburg are investigating the fundamental communication processes that determine multicellular life in humans,
animals and plants. In this way, they aim to gain a higher-level,
integrative understanding of biological signaling processes in order
to develop tailored molecular tools using methods from synthetic and
chemical biology to precisely control signaling processes. In this way,
the researchers seek to develop strategies for the treatment of cancer
using immunotherapies or for resource-conserving crops production, among
other things. Maximilian Ho"rner and Wolfgang Schamel are group leader in
the Cluster of Excellence, Wilfried Weber is a member of the speaker team.

========================================================================== Story Source: Materials provided by University_of_Freiburg. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Maximilian Ho"rner, Carolina Jerez-Longres, Anna Hudek, Sebastian
Hook,
O. Sascha Yousefi, Wolfgang W. A. Schamel, Cindy Ho"rner, Matias D.

Zurbriggen, Haifeng Ye, Hanna J. Wagner, Wilfried
Weber. Spatiotemporally confined red light-controlled gene
delivery at single-cell resolution using adeno-associated
viral vectors. Science Advances, 2021; 7 (25): eabf0797 DOI:
10.1126/sciadv.abf0797 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/06/210617115523.htm

--- up 5 weeks, 6 days, 22 hours, 45 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1337:3/111)