RPM-Drive: A robust, safe, and reversible gene drive system that remains functional after 200+ generations

TL;DR

This study demonstrates that the RPM-Drive gene drive system remains functional and stable after over 200 generations in Drosophila, showing resilience against mutational breakdown and potential for broader application.

Contribution

It provides the first long-term empirical evidence of a synthetic gene drive's robustness, highlighting its stability and potential for safe, reversible, and adaptable use in various species.

Findings

System remains functional after 200+ generations

Disruptions are likely removed by natural selection

System stability linked to ribosomal proteins and cellular defenses

Abstract

Despite the advent of several novel, synthetic gene drive mechanisms and their potential to one-day control a number of devastating diseases, among other applications, practical use of these systems remains contentious and risky. In particular, there is little in the way of empirical evidence of the long-term robustness of these synthetic systems against mutational breakdown. Rather, most existing systems are either known or predicted to be susceptible to rapid inactivation, though methodological designs continue to be refined. Here we evaluate a currently existing synthetic, underdominance-based gene drive system 200+ generations after it was first established in a laboratory colony of Drosophila melanogaster. Not only do we find that the system is still functioning as designed, we also show evidence that disruptions to the genetic construct are highly likely to be removed by natural selection, contributing to the system's robust, long-term stability. This stability appears to be a result of a fundamental relationship between ribosomal proteins (a novel target of the system) and natural cellular defenses that protect against cancer development. As far as we are aware, this is the longest continually functioning synthetic gene drive system thus verified, making it highly appropriate for additional research into its eventual suitability for field trials. Due to inherent properties of this gene drive, it is also likely to be adaptable for use in many different species. The insect lines established and used to test this system have been deposited at a Drosophila stock center, and are available to labs for further, independent testing.