Leucine aminopeptidase1 controls egg deposition and hatchability in male Aedes aegypti mosquitoes.

Aedes aegypti are vectors for several arboviruses infecting hundreds of millions of people annually. Controlling mosquito populations by regulating their reproduction is a potential strategy to minimize viral transmission in the absence of effective antiviral therapies or vaccines. Here, we demonstrate that leucine aminopeptidase1 (LAP1), detected by a SWATH-MS-based proteomic screen of female spermathecae, is a crucial determinant in mosquito population expansion. Mitochondrial defects and aberrant autophagy of sperm in LAP1 mutant males (LAP1 -/- ), prepared using CRISPR/Cas9 system, result in a reduction of reproduction in wild-type females that mated with them. The fitness of LAP1 -/- males is strong enough to efficiently transmit genetic changes to mosquito populations through a low number of hatchable offspring. Thus, LAP1 -/- males represent an opportunity to suppress mosquito populations and further studies should be undertaken to characterize LAP1's suitability for gene drive usage.