Recent advances in genome editing technologies, also known as gene editing, have made it possible to precisely manipulate the sequence of the human genome to achieve clinical therapeutic effect, such as in gene and cell therapies. This can include correcting disease-causing mutations, adding therapeutic genes to specific genomic sites, and deleting deleterious genes or genomic sequences that increase an individual’s susceptibility or susceptibility to a certain disease. Gene editing is being explored in a wide range of diseases, including rare monogenic diseases such as sickle cell disease, haemophilia and cystic fibrosis, as well as for the treatment and prevention of complex diseases such as cancer, cardiovascular disease and human immunodeficiency. virus.
Gene editing involves the use of enzymes (or nucleases) to cleave genomic DNA to generate site-specific double-strand breaks (DSBs). These are mainly repaired by non-homologous end joining (NHEJ) or by homology-directed repair (HDR). NHEJ is a popular strategy and results in loss of function of targeted genes by introducing a frameshift into the open reading frame (gene knockout). HDR is used to a lesser extent and involves the use of additional DNA to create a desired sequence in the genome (gene activation).
The three main gene editing techniques used today include zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and gene systems (Cas) with regularly spaced short palindromic repeats ( CRISPR)/CRISPR. Earlier techniques such as ZFNs and TALENs are not used as much as CRISPR due to their low specificity for off-target side effects. The CRISPR-Cas9 system, which was first discovered around 10 years ago, has revolutionized gene editing as it is a faster, more efficient, more accurate and more cost-effective technology.
Since 2012, the number of venture capital (VC) deals for companies developing gene-editing technologies has increased significantly. Analysis by GlobalData’s Pharma Intelligence Center shows that the number of venture capital deals has increased from just one deal in 2012 to 29 deals in 2021, while the total value of venture capital deals since 2012 has reached more of $3.2 billion. Over $1.3 billion was raised in 2021 alone, more than 250% more than what was raised in 2020 ($500 million). Of the 97 venture capital deals identified since 2012, 74 of them involved CRISPR technology, of which 31 closed in 2020 (13 deals) and 2021 (18 deals), respectively (Figure 1).
According to the analysis, Mammoth Biosciences has received the largest venture capital funding, totaling $240 million, from three funding rounds since 2020. This includes a $150 million Series D, led by Redmile Group, which the company plans to use to expand its toolbox of upcoming first-generation CRISPR systems, including proprietary ultra-small Cas14 and Casɸ CRISPR systems for in vivo gene-editing therapies. This follows a $45 million Series C in December 2020, which included participation from Amazon, as well as a $45 million Series B in January 2020. The company has now achieved unicorn status, with a valuation of over $1 billion. Mammoth Biosciences has also forged several recent high-value strategic partnerships with pharmaceutical companies. For example, on January 10, in a deal estimated at over $1 billion, Bayer and Mammoth Biosciences announced a strategic collaboration and option agreement for the use of the latter’s CRISPR systems to develop in vivo gene editing therapies. This will strengthen Bayer’s novel cell and gene therapy platform, and the initial focus of the collaboration will be on diseases targeting the liver.
Other large companies that have raised the most venture capital funds include eGenesis ($225 million), Arbor Biotechnologies ($215 million), Graphite Bio ($195 million), Caribou Biosciences ($169 million). dollars), Beam Therapeutics ($135 million), and others (Figure 2). Arbor Biotechnologies’ $215 million Series B funding round in November 2021 is the largest venture capital funding round in gene editing to date. The company intends to use the funds to advance its liver and central nervous system programs toward clinical trials and advance a pipeline of precision-editing therapies, while continuing to invest in the development of next-generation gene-editing technology.
Investments by pharmaceutical companies in gene-editing companies also increased in 2021, with six venture capital funding deals found. Since 2014, the pharmaceutical industry has only participated in one or two venture capital funding deals each year, with the exception of 2015, where four venture capital deals involving the pharmaceutical industry were found. In terms of the number of venture capital deals, Novartis and Bayer lead with four and three deals respectively. Novartis appears to have been an early investor in gene-editing technology, with four venture capital deals between 2014 and 2016, but does not appear to have participated in any such deals since then. Examples of pharma investments in gene-editing companies in 2021 include Vertex (Arbor Biotechnologies, $215m Series B), Bayer (eGenesis, $125m Series C), and AbbVie (Caribou Biosciences , $115 million Series C). Other companies that have invested in gene editing companies include Novo Nordisk, Eli Lilly, Takeda, Lundbeck, WuXi AppTec, Biogen, Celgene and GlaxoSmithKline (GSK). All deals with pharmaceutical participation have involved companies developing CRISPR-based gene-editing technology.
In 2021, there were several major clinical milestones in gene editing. For example, Intellia Therapeutics announced the first data from an in vivo CRISPR therapy for the treatment of transthyretin-mediated (ATTR) amyloidosis. NTLA-2001 reduced serum levels of transthyretin, a harmful hepatic protein, by 87%, compared to standard therapy typically achieving an 80% reduction. CRISPR Therapeutics and Vertex Pharmaceuticals announced data for their gene-editing therapy for sickle cell disease, which showed that all 15 beta-thalassemia patients treated were transfusion-independent and all seven sickle-cell patients were seizure-free. vaso-occlusives. Additionally, in July 2021, the World Health Organization released a series of reports that provide the first global recommendations to help establish genome editing as a tool to address public health concerns, highlighting the emphasis on safety, efficiency and ethics.
Advances in gene editing technologies have opened up exciting new avenues in drug discovery and medicine. The enormous potential of gene editing techniques, such as CRISPR, is beginning to be realized in terms of treating rare and complex diseases. GlobalData expects to see increased activity in this space in the coming years, including new investments in companies developing gene-editing technologies.