US 11,739,370 B1
Methods and compositions for in vivo screening of therapeutics through spatial transcriptomics
Martin Borch Jensen, San Francisco, CA (US)
Assigned to Gordian Biotechnology, Inc., San Francisco, CA (US)
Filed by GORDIAN BIOTECHNOLOGY, INC., San Francisco, CA (US)
Filed on Jan. 7, 2021, as Appl. No. 17/144,046.
Claims priority of provisional application 62/959,699, filed on Jan. 10, 2020.
Int. Cl. C12Q 1/6823 (2018.01); C12N 5/071 (2010.01); C12Q 1/6869 (2018.01)
CPC C12Q 1/6823 (2013.01) [C12N 5/0602 (2013.01); C12Q 1/6869 (2013.01); C12Q 2563/185 (2013.01)] 18 Claims
 
1. A method for identifying a candidate therapeutic moiety comprising:
(1) administering to an animal or an organoid a library of expression cassettes comprising:
(a) a plurality of nucleic acid sequences, each encoding a different therapeutic moiety operably linked to a therapeutic moiety barcode; and
(b) a plurality of nucleic acid sequences encoding one or more reporter constructs that alone or collectively are indicative of a cell state or a likelihood of a cell state of the cell;
(2) removing a tissue from said animal or organoid and placing a section of said tissue on a coated surface; wherein said surface coating comprises primers encoding a spatial barcode providing coordinates for each of various spots on said coated surface;
(3) detecting a change in a cell state or likelihood of a cell state of one or more cells of the animal or the organoid and coordinating the presence of said therapeutic moiety to a specific cell or location within said tissue section using said spatial barcode,
wherein detecting comprises performing spatial transcriptomic RNA sequencing of a population of cells to determine an amount of the candidate therapeutic moiety present in the population of cells, thereby identifying a candidate therapeutic moiety.