With limited understanding of most new biotechnologies, how do citizens form their opinion and what factors influence their attitudes about these innovations? In this study, we use gene drive biotechnology in agricultural pest management as an example and theoretically propose that given low levels of knowledge and awareness, citizens’ acceptance of, or opposition to, gene drive is significantly shaped by two predisposition factors: individuals’ general orientation toward science and technology, and their specific benefit-risk assessment frame. Empirically, we employ data collected from a recent US nationally representative public opinion survey (N = 1220) and conduct statistical analyses to test the hypotheses derived from our theoretical expectations. Our statistical analyses, based on various model specifications and controlling for individual-level covariates and state-fixed effects, show that citizens with a more favorable general orientation toward science and technology are more likely to accept gene drive. Our data analyses also demonstrate that citizens’ specific gene drive assessment frame—consisting of a potential benefit dimension and a potential risk dimension, significantly shapes their attitudes as well—specifically, people emphasizing more on the benefit dimension are more likely to accept gene drive, whereas those who place more importance on the risk dimension tend to oppose it. We discuss contributions of our study and make suggestions for future research in the conclusion.