From 1965, while still working for Mikoyan, Lozino-Lozinskiy led the super-secret project, designated Spiral, which was one of the early Soviet attempts to develop a small manned space plane.

This mini-shuttle would be launched on the back of a hypersonic aircraft, itself capable of reaching Mach 6 (or six times of the speed of sound). After separation from the carrier aircraft, the Spiral would be boosted into orbit by a detachable rocket stage.

Although several prototypes of the Spiral space plane had been build and tested in atmospheric flights, the program was terminated in favor of much more ambitious Soviet effort, aimed to respond to the development of the Space Shuttle in the United States.

In 1976, Lozino-Lozinskiy was put in charge of NPO Molniya, a newly created design center on the outskirts of Moscow. The organization had the unprecedented task of developing a 100-ton reusable orbiter with the capabilities similar or exceeding those of the US Space Shuttle. Unlike the US Shuttle, the Soviet winged orbiter would ride into orbit on a super-heavy booster developed separately at NPO Energia.

Known as Buran, the Soviet shuttle made a single unmanned orbital flight and completed the world's first automated landing in 1988. However with the collapse of the Soviet Union in 1991, the Buran program was cancelled due to lack of funding.

After demise of the Buran, Lozino-Lozinskiy led NPO Molniya in the search of a new mission. Along with the development of lightweight airplanes, the center proposed a number of unconventional aerospace systems aimed at reducing the cost of launching commercial payloads into space. A small reusable space plane, developed under Lozino-Lozinskiy's leadership during the 1990s was designed for launch on top of the giant Antonov-225/Mriya aircraft. Known as MAKS, or Multi-purpose Reusable Aerospace System, the spacecraft never made it beyond the design stage.