Gene therapy pioneer James Wilson's team has found new ways to reduce the toxicity of gene therapy

However, experiments in non-human primates (NHP) have found that gene therapy targeting the central nervous system can be toxic in the back root nerve section (DRGs), leading to the development of ataxia.
, a team led by Professor James Wilson, a renowned pioneer of gene therapy at the University of Pennsylvania, found that using microRNAs to regulate genetically modified expressions in DRGs eliminates DRG toxicity caused by gene therapy.
researchers say the findings could lead to the development of safer gene therapies to treat diseases of the central nervous system.
study was published in Translation ScienceAl Medicine.
the use of adeno-related viral vectors in non-human primates to deliver gene therapy through spinal fluid or intravenous infusion has shown that certain nerve bundles in the spinal cord and outer nerves have axon mutations.
can be traced back to the back root nerve cells, small groups of nerve cells located outside the spinal cord that transmit sensory information.
also found that common immunosuppressants do not eliminate this toxicity, and further studies have shown that this toxicity is due to the genetic modification carried by the multi-expression gene therapy of nerve cells in DRGs, which causes stress reactions in cells.
study, researchers used a gene expression regulation mechanism in DRG neurons.
microRNA complex called miR183 is expressed in DRG neurons.
this microRNA is mainly expressed in DRG and can specifically reduce gene expression in cells.
researchers inserted the target sequence of miR183 into the genetically modified 3' non-transcriptional region carried by the AAV carrier.
they found that the modification reduced the level of expression of GM in DRG neurons by about 80 percent without affecting GM expression in other areas of the brain.
adding miRNA target sequences to the 3' non-transcriptional region of GM can use miRNAs in DRG cells to reduce the expression of GM and protect DRG neurons (Photo: Credit: Generapy Program, University of Pennsylvania) Reference: s1? Hordeaux et al., (2020). MicroRNA-mediated inhibition of transgene expression reduces dorsal root ganglion toxicity by AAV vectors in primates. Science Translational Medicine, DOI: 10.1126/scitranslmed.aba9188 [2] Jim Wilson offers a safer solution to some of the industry's gene therapy woes. Retrieved November 12, 2020, from [3] Researchers develop approach to prevent toxicity tied to neurological gene therapy. Retrieved November 12, 2020, from