Fusosome compositions for hematopoietic stem cell delivery

Abstract

The present disclosure provides, at least in part, methods and compositions for in vivo fusosome delivery. In some embodiments, the fusosome comprises a combination of elements 5 that promote specificity for target cells, e.g., one or more of a fusogen, a positive target cell- specific regulatory element, and a non-target cell-specific regulatory element. In some embodiments, the fusosome comprises one or more modifications that decrease an immune response against the fusosome. 393 20 26 20 54 44 09 J ul 2 02 6 0 9 J u l 2 0 2 6 A B S T R A C T T h e p r e s e n t d i s c l o s u r e p r o v i d e s , a t l e a s t i n p a r t , m e t h o d s a n d c o m p o s i t i o n s f o r i n v i v o f u s o s o m e d e l i v e r y . I n s o m e e m b o d i m e n t s , t h e f u s o s o m e c o m p r i s e s a c o m b i n a t i o n o f e l e m e n t s 5 t h a t p r o m o t e s p e c i f i c i t y f o r t a r g e t c e l l s , e . g . , o n e o r m o r e o f a f u s o g e n , a p o s i t i v e t a r g e t c e l l - s p e c i f i c r e g u l a t o r y e l e m e n t , a n d a n o n - t a r g e t c e l l - s p e c i f i c r e g u l a t o r y e l e m e n t . I n s o m e e m b o d i m e n t s , t h e f u s o s o m e c o m p r i s e s o n e o r m o r e m o d i f i c a t i o n s t h a t d e c r e a s e a n i m m u n e 2 0 2 6 2 0 5 4 4 4 r e s p o n s e a g a i n s t t h e f u s o s o m e . 3 9 3

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