Inhibiting LINE-1 retrotransposons therapeutically in disease
- 1L1 Therapeutics
Abstract
The LINE-1 retrotransposon is a virus-like genomic element that can activate in diseased cells. It has been implicated in cancer, autoimmunity, developmental disorders, infectious disease and neurodegeneration. LINE-1 can be inhibited by reverse transcriptase inhibitors, small molecules originally developed for HIV. The correlation between HIV and LINE-1 inhibition is ∼0.9 on a log scale, in spite of >450 Mya of evolutionary history since retroviruses diverged from retrotransposons. Suppression of HIV requires prevention of a completed 9.7 kb virus insertion into the genome in immune cells. However, every cell in the body already contains >100 copies of LINE-1 that can potentially activate. Even incomplete LINE-1 mediated insertions can cause damaging mutations and genome instability. Furthermore, partial HIV and LINE-1 products in the cytoplasm of cells can contribute to an inflammatory immune response. Preclinical studies have shown LINE-1 inhibitors slow the progression of otherwise unrelated diseases. LINE-1’s contribution to these diseases can potentially be quantified using single-nucleus whole-genome sequencing on diseased tissue, enabling prioritization of disease selection for therapeutic development. Furthermore, LINE-1’s ORF1p protein can be measured in the blood of individuals with certain cancers. LINE-1 inhibitors could therefore be extended to various diseases. Potentially used both as an anti-inflammatory and prophylactically to help preserve genome integrity.
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BibTeX
@misc{brandler2026inhibiting,
title = {{Inhibiting LINE-1 retrotransposons therapeutically in disease}},
author = {William Brandler},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15011180/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15011180/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Inhibiting LINE-1 retrotransposons therapeutically in disease
AU - William Brandler
PY - 2026
DA - 2026/10/28
PB - ChemRxiv
DO - 10.26434/chemrxiv.15011180/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15011180/v1
AB - The LINE-1 retrotransposon is a virus-like genomic element that can activate in diseased cells. It has been implicated in cancer, autoimmunity, developmental disorders, infectious disease and neurodegeneration. LINE-1 can be inhibited by reverse transcriptase inhibitors, small molecules originally developed for HIV. The correlation between HIV and LINE-1 inhibition is ∼0.9 on a log scale, in spite of >450 Mya of evolutionary history since retroviruses diverged from retrotransposons. Suppression of HIV requires prevention of a completed 9.7 kb virus insertion into the genome in immune cells. However, every cell in the body already contains >100 copies of LINE-1 that can potentially activate. Even incomplete LINE-1 mediated insertions can cause damaging mutations and genome instability. Furthermore, partial HIV and LINE-1 products in the cytoplasm of cells can contribute to an inflammatory immune response. Preclinical studies have shown LINE-1 inhibitors slow the progression of otherwise unrelated diseases. LINE-1’s contribution to these diseases can potentially be quantified using single-nucleus whole-genome sequencing on diseased tissue, enabling prioritization of disease selection for therapeutic development. Furthermore, LINE-1’s ORF1p protein can be measured in the blood of individuals with certain cancers. LINE-1 inhibitors could therefore be extended to various diseases. Potentially used both as an anti-inflammatory and prophylactically to help preserve genome integrity.
ER -