Materials and methods for treatment of alpha-1 antitrypsin deficiency

A method for editing the SERPINA1 gene in a human cell, the method comprising introducing into the human cell one or more deoxyribonucleic acid (DNA) endonucleases and one or more guide ribonucleic acids (gRNAs) comprising a spacer sequence comprising an RNA sequence corresponding to a sequence selected from the group consisting of 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;
• thereby to effect one or more single-strand breaks (SSBs) or double-strand breaks (DSBs) within or near the SERPINA1 gene or other DNA sequences that encode regulatory elements of the SERPINA1 gene.