US 11,851,653 B2
Materials and methods for treatment of alpha-1 antitrypsin deficiency
Chad Albert Cowan, Cambridge, MA (US); Roman Lvovitch Bogorad, Cambridge, MA (US); Jeffrey Li, Cambridge, MA (US); Ante Sven Lundberg, Cambridge, MA (US); Matthias Johannes John, Cambridge, MA (US); Jeffrey William Stebbins, Cambridge, MA (US); and Thao Thi Nguyen, Cambridge, MA (US)
Assigned to CRISPR THERAPEUTICS AG, Zug (CH)
Appl. No. 15/779,836
Filed by CRISPR THERAPEUTICS AG
PCT Filed Dec. 1, 2016, PCT No. PCT/IB2016/001845
§ 371(c)(1), (2) Date May 29, 2018,
PCT Pub. No. WO2017/093804, PCT Pub. Date Jun. 8, 2017.
Claims priority of provisional application 62/324,056, filed on Apr. 18, 2016.
Claims priority of provisional application 62/261,661, filed on Dec. 1, 2015.
Prior Publication US 2019/0010490 A1, Jan. 10, 2019
Int. Cl. C12N 9/22 (2006.01); C12N 15/11 (2006.01); C12N 15/10 (2006.01); A61K 9/00 (2006.01); A61K 31/7088 (2006.01); A61K 48/00 (2006.01)
CPC C12N 15/111 (2013.01) [A61K 9/0019 (2013.01); A61K 31/7088 (2013.01); C12N 9/22 (2013.01); C12N 15/102 (2013.01); A61K 48/00 (2013.01); C12N 2310/20 (2017.05); C12N 2320/30 (2013.01); C12N 2320/32 (2013.01); C12N 2800/80 (2013.01)] 5 Claims
 
1. One or more guide ribonucleic acids (gRNAs) for editing a SERPINA1 gene in a cell from a patient with alpha-1 antitrypsin deficiency (AATD), the one or more gRNAs comprising a spacer sequence selected from the group consisting of the RNA sequences corresponding to the full-length nucleic acid sequences in SEQ ID NOs: 55,559, 55,574, 55,575, 55,577, 55,578, 55,584, 55,586, 55,587, 55,600, 55,602, 55,605, 55,607, 55,616, 55,625, 55,627, 55,628, 55,633, 55,635, 55,639, 55,641, 55,642, 55,646, 55,669, 55,671, 55,672, 55,686, 55,688, 55,694, 55,696, 55,701, 55,704, 55,705, 55,708, 55,709, 55,716, 55,718, 55,721, 55,722, 55,724, 55,726, 55,727, 55,730, 55,732, 55,743, 55,744, 55,748, 55,749, 55,751, 55,754, 55,762, 55,764, 55,771, 55,778, 55,781-55,783, 60,476, 60,477, 60,480-60,482, 60,485, 60,487, 60,490, 60,494, 60,496, 60,497, 60,504, 60,506, 60,515, 60,517, 60,519, 60,527, 60,529, 60,539-60,541, 60,555, 60,557, 60,558, 60,564, 60,569-60,572, 60,575, 60,578, 60,581, 60,588, 60,591, 60,592, 60,599, 60,601, 60,605, 60,607, 60,618-60,620, 60,622, 60,630, 60,632, 60,633, 60,637, 60,639, 60,640, 60,642, 60,645, 60,648, 60,657, and 60,660, wherein said one or more gRNAs has a cutting efficiency of greater than 40%.